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Paracetamol (1)

Paracetamol (1)

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BAo cAo KET QuA NGHI~N cUU

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TAl CAP BO

Ten de tal: NGHIEN cmr UNG DUNG PHUONG PHAp sAc KY LONG HI~U NANG CAO (HPLC) VA DO QUANG PHO UV-VIS DE DINH TINH VA DINH LUONG CAC HOAT CHAT TRONG . MQT s6 THUOC CO'Ttr2 DEN 5 THANH PHAN
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Chii nhlem de Uti:

T.S. THAI nUY THIN

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Co quan chu trl: TRUONG DAI HOC nuoc
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HA NOI

Co quan ph6i hop chinh: VIEN KlEM NGHIEM THUDe BO Y Tt . . .

BAO CAO TONG KET DE TAl NGHIEN COO KHOA HOC CAP BO . .
Co quan quan

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Iy d~ Uti: DO Y Tt

CO'quan chiI tra d~ tal: TRUONG I>.;.I HOC DUQC HA N(n

NGHIEN ccu UNG DUNG PHUONG PHAp sAc KY LONG N HI~U NANG CAO (HPLC) VA DO QUANG PHO UV-VIS DE DINH TiNH VA DINH LUONG cAc HOAT CHAT TRONG . MOT s6 THU6c CO·Ttr2 DEN 5 THANH PHAN
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Ten d~ tal:

ChiI nhiem de tal: Thai Duy Thin Danh sach nhUng nguOi thl}'c hi~n chinh:

1. PGS-TS Thai Phan Quynh Nhu 2. NCS-DS Trdn vt« Hung 3. ThS Nguyin TUUngVy 4. ThS vs sn n« 5. ThS Nguyen Tudn Anh, 6. DS CKI Hoang Vein DUe.

ThOi gian thuc hien de mi: Tit thang 1-2003 den thang 12 -2005. Tdng kinh phi dll(_1c duyet: 190.000,000d. T6ng kinh phi dll(_1c Ap: 190.000.000d. c

MUCLUC . NQidung Phin A. TOM TAT cAc KET

.
Trang 1
1 2 2 3

QuA NOI B~T CUA DE TAL 1. K€t qua n6i b?t cua d~ ali.

2. Ap dung vao thirc ti~n xa h9i. 3. Danh gia tlnrc hien de tai d6i chi€u voi de cuong nghien ciru da dtroc phe duyet. 4. Cac

y kien

de xuat.

Phin B. N(n DUNG BAo cAo CHI TIET. 1. D~t vAn d~. 2. Tang quan d~ tai,
2.1. Tinh hinh nghien ciru trong va ngoai mroc. 2.2. T6ng quan

4 4 6
6 6 18 18 18 19 22 23

v8 cac plnrong

phap phan tich.

3. DAi ttrC}'llg phirong phap nghien cuu. va 3.1. Thi€t k€ nghien ciru, 3.2. Chon mftu, ca mdu va d6i nrong nghien ciru. 3.3. Phuong phap nghien ciru. 3.4. Phuong phap xu

Iy s6li~u.

4. KSt qua nghien ciru. 4.1. Dinh tinh va dinh hrong paracetamol, bromhexin hydroc1orid, pseudoephedrin hydroclorid, clorpheniramin maleat va cafein bang phtrong phap HPLC. cs« tri: PGS-TS Thai Phan Quynh Nhu. 4.2. Dinh hrong d6ng thai paracetamol (PA) va acid mefenamic (AM) trong vien nen bao phim Pamesic bang phuong phap HPLC.

23

en: tri: TS. Thai Duy

Thin.

27

4.3. Nghien ciru dinh hrong ddng thai paracetamol (PA) va cafein (CA) trong thu6c da thanh phfuJ bang HPLC. Chil tri: TS. Thai Duy Thin. 4.4. Nghien ciru dinh hrong d6ng thai paracetamol (PA) va ibuprofen (IB) trong thuoc da thanh phan. Chi: tri: TS. Thai Duy Thin. 4.5. Dinh hrong d6ng thai paracetamol CPA) va quinin sulfat (QS) trong vien bao Antigrip F bang phuong phap HPLC. ci« tri: TS. Thai Duy Thin 35 31

38

4. Dinh IUQ11g d6ng thai paracetamol va ibuprofen trong vien nen bang phirong phap toan ph6. o« tri: NCS-DS r-s« vi« Hung.9. Thai Duy Thin. 7. Dinh hrong d6ng thai paracetamol mefenamic trong vien nen Pamesic bing do quang ph6 MeA. 4. cs« tri: TS. ChiLtri: TS. Phl} lue. Dinh lUQ11gd6ng thai paracetamol. Tai li~u tham khao. 87 . clorpheniramin maleat va phenylpropanolamin hydroc1orid b~ng phuong phap HPLC.TS Thai Phan Quynh Nhu. 58 va acid 69 79 85 4.6. 4. Chu tri: PGS.8.7. Thai Duy Thin. ephedrin hydrochlorid va 41 phenobarbital trong thuoc h6n h<JPtri hen suy€n bang phirong phap s~c Icy long hieu nang cao. 46 52 cs« tri: NCS-DS Trim n« Hung. Ti€u de tai 10. Dinh hrong dong thoi theophylin. 8. Dinh IUQ11g Ang thai paracetamol va quinin sulfat trong vien nen d Antigrip F bing phuong phap phan tich da cAutir (MCA).10. 4.

Dang ti~p tuc nghien ctru. •:.. HQi nghi direc Dong dirong IV 1112005 0 Thanh ph6 He. Tom tiit cae . tap chi diroc hoc .. n6i b(it .Ch i Minh. nhieu hon mQt cong thirc so voi du ki~n trong d€ cuong nghien ciru. Da khao sat tren 4 cong tlnrc thu6c c6 hai thanh phfut ph6i hQ'P..:. danh gia tren mQt s6 cong thirc thuoc ph6i hep khac..7-. Trong d6 c6 7 qui trinh sir dung plnrong phap HPLC va 3 qui trinh sir dung phirong phap quang ph6 tir ngoai pharr tich da cAu ttl MCA . Da xay dung diroc 10 qui trinh phan tich dinh tinh va dinh hrong cac hoat chAt trong 7 cong thirc thu6c ph6i hQ'Pph6 bi~n tren thi tnrong..... Cac nghien CUutren d€u da duQ'Ccac chuyen gia v€ ki~m nghiem kiem tra.. . .. Chung toi da khai thac. Tham gia 3 hQi nghi khoa hoc qu6c t~: HQi nghi diroc Dong dirong III 5/2003 0 Thai Lan. c. Xay dung duoc phuong phap. .. --_ . b.. (rng dung thanh ceng phirong phap... .__ _.. •:. HQi nghi hoa hoc A Au 0 Ha NQi 10/2003. thfun dinh la co gia tri khoa hoc va y nghia tlurc ti€n. Kit qua C(l thi ..-- PHAN A. hien m dai vito viec kiem nghiem cac thu6c c6 nhieu han mQt thanh phfut hoat chAt.. qui trinh phan tich da xay dung vao viec kiem nghiem mQt s6 cong thirc thu6c c6 til 2 toi 5 thanh phfut hoat chAt.:.. •:..__ oJ tai .1- .. ki~m clnrng va ban lu~ v€ phirong phap lien quan toi cac nQi dung c6 trong de tii cua chung toi.__ ..l anh. GUO ..--_ -..:. nhb trao d6i thong tin. kit .... mo hinh qui trinh phan tich dinh tinh va dinh luong n6i chung d6i voi cac hoat chAt trong mQt cong tlnrc thuoc ph6i hop sir dung hai phirong phap tren . . --... >- TOM TAT CAC KET QUA NOI B~T CUA BE TAl ? X _ ? ~.t ella d@tii a.. Dong gop mUi cila iI2 ta. d~c bi~t la cac thuoc c6 nhieu hon 5 thanh phfut boat chAt. irng dung hai phuong phap phan tich cong C1.2 cong tlnrc thuoc co ba thanh phfut ph6i hQ'Pva 1 cong tlnrc thuoc c6 nam thanh phfut ph6i hQ'P .. va tham gia bao cao trong cac hQi nghi v€ diroc n6i rieng va hoa hoc n6i chung (xem phfut phu luc). K~t qui n6i b..__ cua _ ._____________________ Phdn A. •:. da diroc cong b6 tren cac tap chi chuyen nganh nhu tap chi kiem nghiem thuoc. d6 la phirong phap HPLC va phirong phap Quang ph6 tir ngoai phan tich da cAu tir MCA. ---. sre dung thu~t toan th6ng ke trong viec danh gia cac k~t qua phan tich . vi nghien CMU khoa hfJc 12 cong trinh khoa hoc co lien quan da dircc cong b6. 1. .

MQt s5 chirong trinh dang diroc cac co so tham khao d~ xay dung tieu chuan cho san phAro cua minh. trong d6 co 3 nh6m sinh vien tham gia bao cao tai hQi nghi khoa hoc tu6i tre cua tnrong. diroc vi~n kiem nghiem va m{>ts6 trung tam kiem nghiem img dung de kiem tra chdt hrong cac thuAc da thanh phfut dang hru hanh tren thi tnrong. Cac chi tieu khoa hoc dB ra trong dS cuong duoc ton trong va thirc hien ddy duo c. Banh gia v. Ap dung vao thjre tiin sin xuAt va dM sang xi h{)i K~t qua nghien CUu cua chung toi Iii co tinh kha thi va c6 y nghia thuc ti6n. Kit qua l(lo ra so v6i dfl"kiln cua ban td cumrg Cac k~t qua thu diroc hoan toan phil hop voi du kien. D~ tai da t~p hop va huy dQng duQ'c mQt sA hrong 1611 can bQ tre cua tnrong D~ hoc diroc Ha nQi~Vien kiem nghiem thu6c va mQt s6 Trung tam kiem nghiem dia phirong tham gia. b. C6 12 sinh vien lam cong trinh t5t nghiep phuc vu cho nQi dung d~ tai. 1 sinh vien tham gia bao cao hQi nghi diroc dong duong. hieu qua. Gop phfut dao tao diroc 2 thac _ sy duoc hoc va mQt diroc sy chuyen khoa cdp 1. . chi tiBn dS tai theo dung qui dinh. MQt s6 sinh vien sau khi t6t nghiep da phat huy t6t chuyen mon thanh) .?c sir dpng kinh phi Da sir dung kinh phi dung muc dich. 3. gop phfut nang cao trlnh dQ va kinh nghiem chuyen mon cho cac can bQ. con thuc hi~n them diroc 1 cong tlnrc so voi dS cuong. trung tam ki~m nghiem cac tinh. Dauh gia thVC hifn di tai dai chi@u v6i di CVO'Dgughien ctiu di dtrqc phe duyft a.:. Htrong a noi cong tac (vien kiem nghiem thuoc. •:. tu« d{j hodn thdnh DS tai hoan thanh dung ti~n dQvS thoi gian dang kY. MQt s6 chirong trinh diroc nghien cuu la de ap dung lam tieu chuan cho cac co so.. •:. •:. dan nhieu sinh vien tham gia thuc nghiem khoa hoc phuc vu cho dS tAi co k~t qua. 2. d. ThVChifn cdc mflc tiiu nghien cu-u Da hoan thanh ddy dU theo muc tieu va cac nQi dung nghien ctru dllQ'ChQi dang khoa hoc cua be>phe duyet. phong kiem nghiem xi nghiep.2- .'!!_~4~ _! _~~~_M~ _1)_4!_k(iL~~q_~~_!!!~ _q_~!! d: Dong gop dao t(lo can b{j cho nganh ._?~4'!_:1~ t!.

Ti~p tuc rna rQng kSt qua nghien CUu cho mot s6 thuoc co nhieu thanh phful hoat chdt hem. tiSp we danh gia cac phirong phap. qui trinh va k~t qua thu duoc._q_. •:._r~1J_4~r. d~c biet la plnrong phap quang ph6 ill ngoai phan tich da cAu ill MCA. the -3- . Cae y kiin d~ xuit .l' quan tam cua BQ Y t~ va cac co quan de d€ tai co duoc ap dung rQng rai hem va rna rQng cho nhi€u san phAro khac. Chung t6i se tiep tuc nghien ci'ru d~ hoan chinh va rna rQng hem trong nhtrng d€ tai khac. TiSp tuc nghien ciru.!!_ ~4~ ~UIl!~_1}_4!_!!_ti_~ ~q_~~_!?!~ _ £~~_ £ . RAt rnong ducc S1. 4.:. jrng dung hai phuemg phap dAxay dung cho nhi€u cong thirc Ian thuoc da thanh phAn khac. irng d1J11g nhieu hem trong thuc ti~n d~ co co sa d~ nghi dua rnQt s6 chuyen luan thu6c da thanh phftn vao duoc diSn Viet Nam trong xudt ban too. •:.

. thu6c nho mAt h6n hQP. XuAt phat tir yeu cau thuc tS va cAp thiSt do. x X.D. •:. 3 nhom thu6c nhir vitamin voi thu6c ha nhiet. v . tren the gioi. -4- . III). thu6c dung ngoai hem hop v. thi wang doanh. Cling co th~ k€t hQP cac hoat chAt cua 2.. M\lC tieu nghien Ctlu . Cac thudc ngoai duqc cAp sd dang Icy hru hanh ngay cang nhieu. thu6c chong lao V. Tinh cAp thi~t cin nghien Ctlu cua d~ Ud san xudt va kinh Trong nheng nam gAn day. dira tren phirong phap HPLC va phirong phap quang phd tlr ngoai phan tich da cAu tlr MeA .mg dpng phrmng phap sdc kj long hi?u niing cao (HPLC) va do quang phD UV. cac thu6c co nhieu thanh phfut dang diroc san xuAt va sir dung ngay cang nhieu.N. Vi viY. tieu chuan cho cac thu6c loai nay vao duoc di6n trong cac Ian xuftt ban toi lit rAt cfm thiet. vi~c nghien ctru d~ dira m{>tsf. i:J mroc ta.2..1. Trong s6 do.fi_~_~4~!!~ . D~ ph6i hop tac dung diroc Iy trong m{>tch€ pham thu6c va ti~n sir dung cho benh nhan. hien da co khoang 6 nghin m~t hang thu6c trong nuoc va khoang 4 nghin thu6c ngoai nh~p (iroc tinh co tren 800 hoat chAt) dang hru hanh tren thi tnrong Viet nam.. H~T TAIcApBQ vAN DE thuoc dang phat trien nhanh ca v~ 1.. thuoc s6t ret.V. cac nha nghien ciru v€ kiem nghiem va cac co quan quan Iy chAt hrong thuoc. Xay dung qui trinh phan tich m{>t s6 thu6c da thanh phfut dB: chon (chua co tieu chufut hoac co tieu chudn nhimg chua dAy du hoac co nhuoc di6m). cac vitamin..Vis ttl lIinh tinh va djnh lurmg cac hopt chat trong m{jt sa thuac co til' 2 din 5 thanh ph8n" 1. chung toi dii tiSn hanh nghien ciru d~ tai: "Nghi2n CNU ._!_·__1?.v . Noi chung. gop phdn nang cao chAt hrong thucc hru hanh tren thi wang.:. hau nhu chua co cac chuyen Iu~ ve thuec nhieu thanh phAn. cac thu6c da thanh phfm dB: va dang chiem m{>t tY Ie cao. khang sinh voi thu6c chong viem. " PHAN B. NQI DUNG BAO CAO cm TIET KET QUA NGmEN 2. ? A CUuDE 1. thu6c da thanh phfm thirong duqc ph6i hop cac hoat chAt trong cung m{>t nhom thuec nhir: cac khang sinh. Nhu v@y viec nghien ciru phirong phap kiem nghiem cac thuoc da thanh phfm 1ft m{>tviec rAt cfm thiet d6i voi cac nha san xuAt.. cac thu6c ha nhiet giam dau. . Ap dung cac qui trinh tren d~ ki~m nghiem cac thuoc da thanh phAn co cong thtrc ttrong 1\1'. Trong diroc di~n Viet Nam moi nhAt (D. Theo th6ng ke cua C\lC quan Iy Duoc Vi~t Nam.

pseudoephedrin hydroclorid.~~_'!41J_!!~ •:.l·L-t (L '£~ t\A~ t-~~: [L~ ~ f'{_ c.._!. brornhexin hydroc1orid va clorphenirrarnin maleat. d6la cac thuoc han hQ'Psau: Thu6c c6 2 thanh phfuI + Paracetarnol va cafein. ephedrine hydroclorid va Phenobarbital.... cafein.A ) tr ) . + Theophyllin. d. -5- . Muc tieu nghien CUll cu th~ Trong pham vi 1 d~ tai - ..__l?. Thuoc c6 3 thanh phdn {Ul. + Paracetamol va quinin sulfat. Thuec c6 5 thanh phan +Paracetarnol.. clorphenirrarnin maleat va phenylpropanolarnin hydroclorid. t p4:_ 1Af MLC~ML C <UCW-[ (-'\l1L{ _ ) + Paracetarnol.. + Paracetarnol va ibuprofen.p bo chung toi chon mot s6 cong thirc thu6c c6 ill 2 den 5 thanh phlin d~ nghien ciru (da diroc bOphe duyet).

cac ch€ phfun thuoc da thanh phfin duqc nghien ciru rAt nhieu. dang ti~u phan hoac mQt chAt long phu len mQt chAt mang rAn hay mQt chdt mang dd duoc biBn dbi bfutg lien kBt hoa hoc voi cac nhom htru ca. Tren the gioi. phan bd. Pha tinh chua trong cQt 1(\mQt chAt rAn dd direc phan chia duo. TONGQUANTAILIBU _ 2. 27. USP 27 . a Vi~t Nam ta dd co nhi~u cong trinh nghien crru a cAp co nghiem cac thuoc da thanh phfin nhir: tan trong mroc va vitamin tan bang phuong phap HPLC [10].1. A dd co nhtmg hQi nghi v~ cac phuong phap kiem nghiem ngoai diroc di~n. -6- . 28] . Tinh hinh nghien eu-u trong va ngoai nwe sa va cAp bQ v~ ki~m Nghien Trong nhtrng nam qua. EP. JP.!_!~~_~~~~ 2. Pha dQng 1(\chAt long chay qua cQt voi mQt t6c dQ nhdt dinh. TAng quan vi eac phuong phap phan tieh 2. Khai ni?m sac kY long hi?u nang cao La mQt phtrong phap tach hoa ly dua vao ai hrc khac nhau cua cac chAt khac nhau voi hai pha luon tiep xuc va khong dang tan voi nhau. 25. trao dbi ion hay ray phan ttl. USP. nhirng phan 160 chi dirng a mire tieu chucln co sa. ciru dinh lUQ11gd6ng thai cac vitamin trong dAu trong thuec h6n hop multivitamin - Nghien cuu irng dung quang ph6 UV-VIS. con rdt nhieu nQi dung cfin phai duqc nghien ciru d~ img dung trong thirc ti€n.. 23. Rieng duoc di~n nhiet giam dau . 8]..1.2. Qua trinh site kY x~y ra co th~ thea cac co ch€: hftp phu. ) co sd thudc da thanh phfin nhieu nhom thudc ha hon va t~p trung vao mQt s6 nhom thuoc ph6 bien nhir: cac vitamin._~·__!_4~g_q~l!_. nhir cac My (USP 23.. Trong cac duoc di~n 160 va thong dung nhir BP... chu yeu ghi cac dang thudc dan thanh phan.. 2. quang ph6 dao ham de dinh hrong cac thuec da thanh phfin [7.. Cac mroc trong khu V\lC Dong Nam thuoc tiem lidocain va adrenalin ...2. Phu01Ig ph tip siic kj long hifU nang cao (HPLC) a.] . Diroc dien Anh (BP1998 va BP2000) co ghi mQt s6 thuoc da thanh phk chuyen lu~ thudc multivitamin. USP 24. Qudc t€ [19. 24. Phap. mQt pha dQng va met pha tInh. T6 clnrc Y te the gioi cling dd co nhtrng chirong trinh d~ t6 chirc hoc t~p va trao d6i gitra cac nuoc v~ vdn d~ nay. Nghien ciru dinh hrong dang thoi cac hoat chAt trong mQt s6 thucc ha nhiet giam dau bang phirong phap HPLC [6. so voi tdc dQ phat tri~n cua thi tnrong thudc hien nay thi chua du dap img. Tuy nhien..

..__·•••• _ ..._-_ ..ian lltu .1 I .~ ..--.... thai gian hru cua m6i chAt la hang dinh va cac chAt khac nhau thi thoi gian hru khac nhau tuy thuoc vao ban chat._.. ___________~ -------.. '''.f 0 • rIA A Trong qua trinh sAc Icy luon co su phan b5 cua chAt tan gitra pha dQng va pha tinh... "-------·-. ...thoi gian hru thuc (thoi gian luu hieu chinh)..-------..I . Khi pha dQng chay qua cQt vm mQt t6c de) khong d6i thi thai gian hru co th~ thay th~ bang th~ tich hru..:..to Trong do: t'R hi.~--._---.l _---_ . ----. Trong cung mQt di~u kien sAc kY eta chon..~--~. S\!..~~--------------.._x'_4~gq~q_'!_~~~X~~1}_ b.phan b6 nay dtroc d~c trung boi can bang phan b6 voi h~ s6 phan b6 duoc tinh theo cong thirc sau: K= Cs CM Trong d6: Cs. Vi v~y thai gian hru la d~i hreng dinh tinh cac chat. siic ky db cua hai chAtva cac thong s6 d@ctnrng . Thbi .. :i Hinh 1..K ••• LIe so p h an b. .. cAu tao va tinh chAt cua chAt do.-._?_.. va thi coo qua trinh sAc 10/ tich lltu Thai gian hru cua mQt chAt la thai gian tinh til Iuc tiem mdu vao cQt d~n khi chAt do ra khoi cQt dat gia tri nAng dQcue dai va cho pic tren sAc kY dA_ N~u goi tR la thoi gian hru gift cua me)tchAt thi : t' R = tR ..._ ..:t . 10la thai gian ch~t (thai gian khong hru gift)...~~----------1· lIOl... eM la nAng de)cua chAtphan tfch trong pha dQng va pha tinh 6 thai di~m can bang.... .. Th~ tich luu la th~ tlch pha dQng thu duoc sau cQt trong khoang thai gian nrong irng voi thoi gian hru.. ~ .W. Cdc ilQiltamg ilgc trung .. -7- ...._.--..._-_.~......6.

chieu cao dla 19 thuyet (H) va s6 dia 19 thuyet (N) lit hang dinh d6i voi m6i chAt phan tfch. nhu v~y a luon 16'11 han 1. C6 the tlnh k' thea mQt cong tlnrc khac: .~~!1. nrc lit tY sA gitra IUQ'IlgchAt tan trong pha tinh va IUQ'Ilg chAt tan trong pha dQng a thoi diem can bang k'== Qs == Kx Vs QM VM Trong do Qs. a==-==-= KB sb chon IQc cho r. QM lit hrong chAt tan co trong pha tinh va pha dQng. V s. Thira _ sa dung /U'(!IIg Thira s3 dung IUQ'Ilg lit d~i IUQ'Ilgbi~u thi khll nang phan bb cua chdt tan trong hai pha cQng vai strc chua cua cQt.!_~~~!.5 d€n 2 .. Sa ilia IVthuv2t va ehi2u eao ilia IV thuv2t Hieu hrc cQt tlnrong diroc bieu thi qua hai thong s6: se rna Iy thuyet (N) hoac chieu tAng su phan cao dia ly thuyet (H).V M lit the tich pha tinh va pha dQng. Chieu cao cua dia Iy thuyet dugc tinh thea cong tlnrc: H=!::. Chien rQng pic do (] mra chieu cao pic.. k'A I RB -10 IRA -10 KA I'RB ==I'RA o day ta quy uoc chAt B bi hru gift manh han chAt A. Tlnrong phan tich trong dieu kien a thi trong khoang 1. . h~ bi~t hieu qua tach cua h~ thbng sAc kY. 86 dia ly thuyet N diroc tinh theo cac cong thirc: N ==16 X (!!L)2 W hoac 5.:. M6i tAng dUQ'Cgill lap pha tinh co chieu cao H.54 X (_!L_)2 ~/2 Trong do W ~/2 : Chieu r{>ngpic : a day pic. N V6'i mQt dit~u kien sAc kY nhAt dinh. CQt sAc ky diroc coi nhu co N tAng Iy thuyet. •:. -8- . a cang 16'11 kha nang tach cua hai chAt CMg ro. Trong do L la chieu cao cua CQtsAc ky.:. Hi sA ehvn lee Hai chdt chi diroc tach ra khi chung c6 cac gia tri k' khac nhau._Lr4~g_p'!'f!_. Dfa ly thuyet dircc dinh nghia nhu lit mQt khu V\lC cua h~ thong phan tach mit trong do thi€t l~p mQt can bfutg nhi~t dQng hoc gina n6ng dQ trung binh cua chAt tan trong pha tinh va trong pha dQng. dinh nlnr mQt a m6i b6 chAt tan vito hai pha lai d~t den mQt trang thai can bang moi.

tRA } W. Detector. A. : Tac dQ dong pha dQng.. n6 duoc tinh theo cong thirc: T=Wz 2A Trong d6 Wx: la dQrQng day pic do a 1120chieu cao ella pic. = 2xVRB -tRA) WA+WB 1. C: M6 ta anh huang cua c.:.. B. CQt tach (pha tinh). C : Cac h~ s6 thay d6i phu thuoc vao tirng CQtsAc kY.:. A : la khoang each til dirong vuong g6e ha til cue df._ __ __~ _. DQ phan giai ella hai pic canh nhau diroc tinh theo I trong 3 cong thirc sau: s. PhU'dng trinh Van-Deemter Phuong trinh Van-Deemter mo til anh huang ella tac dQ dong pha dQng va cac thong s6 dQng hoc khac d~n hieu hrc cua CQtsAc kY H=A+-+Cxu u B H u : Chi8u cao rna ly thuyet.__ _ __ __ __ __ _ L . Be Dhlin cidi (R~ DQ phan giai la d~i hrong bieu thi dQtach ella cac ehAt ra khoi nhau trong mQt di8u ki~n sitc Icy da cho.•0'. B(>phan tiem mdu: tiem vao cQt mQt the tich mdu nhAt dinh. He sa dJi xfmg (V Cho bi€t mire dQ can d6i cua pic sAcley. Trong d6: B/u: M6 ta anh huang cua su khuech tan doc cua cac phan tiT chAt tan theo phirong dong S1)' chay cua pha dQng (longitadinal diffussion).. •:.licua pic d€n chan dirong cong phia tnroc.. 2..18 x {tRB .'2(A) + WII2(B) ho~c --x a-I k' a l+k' B B x4 -IN . Bam cao ap: dAypha dQng qua CQtsAc ley. T6nq quan tai lieu . H~ thang may HPLC c6 cac bQph~ chinh sau: -9- . chuyen khai (mass transfer). 6 tai 1120chien cao pic . A: M6 Ul anh huang cua su khuech tan xoay (eddy diffusion). H~ th6ng HPLC: ~ Binh chua dung moi (pha dQng).__. May ghi tin hi~u hoac may vi tinh.

6. 2. B{} tiem mdu 1\1' d{}ng(Autosampler). 3. N61A nhirng ch~t rAn. Khdi ni€m Pha tinh trong HPLC lei chAt nh6i cQt d€ lam nhiem vu tach mQt h6n hop chAt phan tich. •:.:. Can cir theo c~u tnic x3p cua pha tinh la cac hat rAn. kich tlnroc hat rAt nho. . BQ du6i khi chan khong (Vacuum degasser).10- .10 um. phan b6. Bam cao ap (Pump). ngiroi ta chia n6 thanh nhieu loai nhu hAp phu. --Hlnh 2. c6 cac loai: sAc Icy pha C\lC con pha dQng it phan eire). Can cu theo de) phan thuan (pha tinh phan d6i ion. 5. n~u pha tinh hi chAt rfuI ta c6 sdc long ta c6 sdc Icy long-long (LLC). dien tich b~ m~t hat thuong ill 50 ~ 500 m2jg . Can cu theo trang thai rAn hay long cua pha tinh._?__!4~g_!J!I_l}_. ngtroi ta chia n6 thanh hai loai. dirong kinh ca hat ill 3 . Cac thanh phfut co ban cua mQt may s&ckY long hien dai -_ - -- 1_Khay chua binh dung moi (Solvent cabinet). Phiin loai Can cu theo ban chAt chinh cua qua trinh sAc kY trong cQt tach. sAc ky pha dcio (pha tinh it phan cue con pha dQng thi phan cue). Module di~u khien (Control module). sdc kY pha dao tao c~p ion va sAc Icy trao loai Ia xop toan phan hat va xop b8 m~t hat (xop chi lap v6 ngoai). Pha tinh . nguoi ta chia n6 thanh hai C\lC kY long-ran (LSC). trao d6i ion va ray phan tiro Tirong irng voi loai chAt nh6i nhu th~ nguoi ta co mQt loai sAc kY rieng trong ky thu~t HPLC. 4. d.!_!?!~_~~~~ -------------. n~u pha tinh la chdt cua pha tinh va pha dQng. h~ th6ng HPLC hoan chinh Hlnh 3. x3p. Detector. BQ di~u nhiet cho cQt (Columm compartment). 7.

N6 cling c6 th~ Ia dung dich cac mu5i c6 chua cac chAtd~m.co. C6 de)tinh khiet cao. chAttao phirc . C6 tinh kinh t€ va khong qua hiem . . C6 kha nang tach chon IQc mQt h6n hop chdt tan nhdt dinh trong di~u kien s~c . Hoa tan diroc chAt cAnphan tich.11 - kYo ._?__!4!!g!l¥_q_'!_!?!~_~~f¥_ •:. .:. B~n vtmg thea thei gian. Phil hQ'Pvoi Ioai detetor dung d~ phat hien cac chAtphan tfch. Phai nhanh dat cac can bang trong qua trinh sAcky. mOt pha tlnh Phai tro va h6n vtrng voi cac di6u kien cua moi tnrong sitc kY. Cae ylu ta ehinh can chu V Irong lila chen pha ilOng - Ban chAt cua dung moi lira chon lam pha dQng. de) phan cue cua pha dc)ng cling se hi bien d6i va thuong la tang hi~u quit tach . Pha dc)ng la dung mol dung de rna giai chAt tan (chdt cAn phan tich) ra khoi cQt tach d~ thirc hien mQt qua trinh sAc kY_ Day la mot y€u t6 rAt linh dQng va d€ dang thay d6i.hat phai e.:. Tinh chAtb8 mat phai dn dinh (d~c biet wong d6i dAng nhAt.. . Thanh phAn cac chAt tao ra pha dQng. N6i chung m6i loai sitc kY se c6 cac he dung moi rita giai rieng dS c6 duoc hi~u quit phan tach t5t nhAt. Thai gian hru gift ella chdt tan. •:.N6 quyet dinh thai gian hru gift cac ch~t mau va hi en qua su tach sic Pha dQng c6 th~ anh huang d€n: DQ chon IQc cua he pha. Khai niem . N6 c6 th~ la mQt dung moi hoac h6n hop nhieu dung moi trQn Ifill voi nhau thea nhtrng tY I~ nh~t dinh.Can hang dQng hoc cua su tach phai xay ra nhanh va I@plai t6t. lJiiu kien d6i vu. Rira giai gradient: pha dQng lien tuc thay d6i (do tY I~ cua cac thanh phAn tao nen pha dQng thay d6i) trong su5t qua trinh rna giiti.. Pha dQng la mQt trong nhtrng yeu tA quyet dinh hieu suAt tach sAc ky cua mQt han hQ'Pm§:u. •:. . T6c de)dong pha dQng. la ~c trung x5p cua no).pH cua pha de)ng (d~c bi~t chu •:. Y iJ sAc kY trao d6i ion va sitc kY cap ion) . lJi€u kien iliii vUi mot pha dong Phai tro dAi voi pha tinh. Pha dong . Qua Irinh rira giiii Rihl giii ding dong: pha de)ng khong thay dbi trong su6t qua trinh nra giai. kY nhdt dinh. Luc nay.

hilt chan khong.n diem dau va diem cu6i cua pic dtroc . Phuung phap n6i chunn: La plnrong phap cho them vao miu chuan va miu thir mot IUQ11ghAt khong d6i. DQ phan giai cac chAttrong mQt pha tinh. D~ tinh dien tich pic. •:. g. Dank gia dien tick pic: Dien tich pic cua mQt chAt nrong (mg voi tlmg IUQ11ghAt c nhan ra chinh xac va cho k~t qua tat d6i voi nang dQtrung binh.!1.Do r(lng va S\I can d6i cua pic sAc kY . Voi pic co duong n~n bi nhiBu hoac pic hep thi vi~c xac dinh chien cao pic se dB dang va chinh xac hem vi~c xac dinh dien tich pic. Hic sieu fun . f each ilanh gia pic do. n~u khong nhu nhau khi do voi m6i chAt can c6 h~ s6 hi~u chinh.. Phuong phap nay chi d. •:. - Hieu 19c cua CQttach. Phlrung phap ngo(li chunn: La phirong phap dua tren co sa so sanh m§u chufin va miu thir trong cung di~u kien.:. K~t qua ducc tinh toan dua vao str chenh l~ch nbng dQ (luong chAt chufuJ.. Phuung phtip them chunn: Chu yeu duoc sir dung trong kY thu~t HPLC khi c6 vftn de anh huang cua cac chdt phu (vi du : ta diroc). •:.12- . phirong phap nay chi dung khi co S\1' dap trng cua detector tren cac chAt la nhu nhau. Danh gia chiiu cao pic: Khi pic c6 dang khong dAi thi chien cao pic (khoang each gitra duong n~n va dinh pic) lit mQt dai hrong the dung d€ danh gia sdc tY l~ voi dien tich pic va n6 ding co kY db. Dung dich miu thir diroc them mQt lUQ11g ac dinh chit chuan. Trong HPLC. •:._?_·__!4!!g__q~q_. Cac pic thu diroc cua cll hai dung dich miu thir va x mfiu thir them chAt chufut phai duoc do trong cung mQt dieu kien slic ky. Vi khong khi hoa tan trong dung rndi se 410 bot khi trong detector va gay nhiBu tin hieu. K~t qua cua chAt chua bi~t dircc tinh toan so vci miu chufin da bi~t tnroc nAng dQhoac suy ra tlr direng chuan . Phuong phap nay chi ap dung khi cac chi s6 k' la hang dinh. Tdt ca cac dung moi dung trong HPLC (k~ ca pha d(lng) d~u phai duoc dU6i khi bang each dun nong. hien nay ngtroi ta thuong dung may tich phan di~n ill gAn vol may vi tinh (sai s6 khoang 0. . Phlrung phdp tinh theo phlin tram dien tich pic: Nang dQ cua mftu thir diroc tinh toan dua tren dien tich pic tinh thea tY 1~phftn tram dien tich pic chAt thir tren tAng dien tich toan bQ pic co trong sAc kY db.!_!?!~_~~f. •:. vira va cao .3%). . .5%) hoac may tich phan co hoc (sai s6 khoang 1.:. N6 direc tach hoan toan va co nang dQ gfut bang nllng dQ cua chdt phan tich va co cAutnic hoa hoc nrong tu.them vao) va dQ tang cua dien tich hoac chieu cao pic . Phuong phap nay co th~ dung cho cac pic khong bi troi duong n~n va ca pic co dirong nen b] troi. each tinh kit qua . rna trong cung di~u kien sAc kY n6 co thai gian hru gdn c voi thoi gian hru cua chAt cAnphan tich trong miu thir.

tY 1~( Km..d duqc goi la h~ sf.2C2 + + Kl. 1 =[Klm..Beer: lien he voi nhau A: d{>hAp thu quang tai btroc song A. ta co th~ viet gon lai nhu sau: A = K.nCn . diroc do tren may. dQ hAp thu quang va n6ng dO dung dich co theo dinh lu~t Lambert .nCn + K2. v~ n6ng dQ ( Cn) va n. Phuong phdp quang phD tii"ngo{1iph8n tich iIa c8u tii" (MeA) so lY thuyit .. [C] la rna tr~ n6ng dQ cua cac thanh phAn trong h6n hop.:.n en [A] lit rna tr~n dO hAp thu quang. voi n A2 = Kl.2.n c.1 KL2 •.. C: n6ng dQ dung dich. Gia sir m > n.n •••• ~ •••••••• a 111 ••••••••••• CI x C2 (4) Am Trong do: Km. .2 he sf. A = E.n K2.C (voi K = E..2C2 + = K2_1C1 + K2. diroc xac dinh tnroc bdng each do ph6 cua cac dung dich chuan h6n hop d§ hiet tnroc n6ng dQ. ta se thu duoc h~ g6rn m phirong An sf. Co . v~ h~ sf.l Km.13- .C. K2. d: b~ dAy cf.n Am.4!!g_!l!l_l}_'!_~~~L~~'!: ! a. .2. D~ co th~ giai duoc phirong trlnh (4) ta can phai chuyen rna tr~ thanh rna trin vuong bang each nhan voi rna tr~ chuyen vi cua K. Nguyen tdc chung Co so Iy thuyet cua phuong phap dua tren nguyen Iy "D(j hap th¥ quang A coo mot h6n h(1JJ trong dung dich tai m6t buue song m6i thanh phim tai buac song do".nCn (3) AI A2 = KI. ) (2) Khi de>hAp thu quang duqc do tai m buoc song.2 ". (5) chuyen vi cua K lit [K']m._?__. a bat 10/ bfmg tang do hap thu quang m6i cua Trong dung dich. khi do ta co th~ viet phirong trinh (4) dum dang sau: ehu nh~t [Klm. Neu ta gia sir h6n hop cAn do co n thanh phan thi theo nguyen ly tren ta co: Tai buoc song thit nhcft: Al trinh.2C2 + _ + K1. • .. _ 2. Km. m An sf.I K2.d (1) E: dQ hAp thu rieng tai biroc song A. tY 1~). [K] lit rna tr~ tY Ie.. KI.lCI + K1.1CI + K1.n Al = Kl.n ta diroc Nhan ca hai ve cua phirong trinh (5) voi rna tr~ .c do..

. _-or - . khi d6 ta se c6 h~ n phuong trinh n he nay ta dung phirong al. ---+ [Z]n. au ~.11 ••• a2. ---- ----_. D~ giai loai phap Gauss.nXn= bI + a2. au au ._ . - - - - - - - - - - - - - - - -- - - - _.l a2. tuyen tinh.2x2 + a2.14- . danh gia chat lup?y! cda phlin tich chuan bdng cach ap dung binh phufTllg tAi thiiu va cdc thOng k2 tUfTllg quan Thuat binh phtrong tf.nXn= b2 a1.nXn= b...lx] + a2.l = [T]m... C lit nang dQ chua hiet cdn tim cua rndu tlnr. diSu quan trong la ta cdn phai giai ducc phirong trinh (6) dua tren viec xac dinh rna tr~ qua do de>hAp thu h~ s6 hAp thu [K]m. v~y ta c6 th~ viet phirong trlnh tren duoi dang nhir sau Cn.1I (8) oo Voi gia thiet ~. khi do viec giai he tam giac tren rAt don gian. [Z]n.2 a2.2x2 + A= a2.n A= o a2.t = [T] m. th€ len cac phirong trinh ti€p tren tim ducc Xn-l.1xI + a1. .t Trong thirc te cua bai toan.i thieu (least square method) se lam cho dQ dung trong viec phan tich chuan cao hon vi n6 lam giam thieu S\l' sai khac gitra n6ng dQ tlnrc (entered concentration) va nAng de>tinh toan duqc (calculated concentration). khi s6 plurong trinh hop t6i thieu cua h~ 100 han hoac bAng s6 (kich cO'n x n)..n .m . _ . Trong wang voi m = n.t • •:..n (7) Phuong phap Gauss la phuong phap giai bang each dung cac bi€n d6i sa cAp d~ co rna tr~ h~ sf.2 .Tir phuong trinh cu6i ta se tim duoc xn.2x2 + + al. va Xl a plnrong thull trinh dAu tien ..n. co rna tr~ Xet h~ phuong trlnh Cremer sau: + aI. Cn.__ 2. Gitii he Cremer bdng ohufTIIg ohao Gauss Me>t h~ phuong trinh dai s6 tuyen tinh chi tim diroc nghiem.1x] la he Cremer An va rna tr~ [K] lit rnQt rna tr~ vuong quen thuoc trong dai sf. + a2.n ···a n. Xn.2x2 + + al. a1..2 ••• dua he da cho vS he tam giac co dang: a1. day chinh An (nghia lit ta phai c6 m ~ n). Phlin dch chuan._______ 0..2··· a2.f 0. d~ xac dinh nbng de>chua hiet cua rndu tlnr.l -1 (6) Nhir v~y.nthong Am.nxn= b2 he sf. •:. Tone quan fai li~u _ .

n. nghiem. v~y chung ta g~p bai toan t6 hop ch?p n cua p ph§n tiro Theo cong thirc tinh t6 hop ta co: p! nL(p-n)! (9) p Ket qua la ta se co thu duoc . Neu gia thiet chi do tai hai btroc song thi se co phuong trinh.15 - (10) .2C4 s6 cdu tU (p>n}". Theo dang rna tr~n cua h~ (4) 6' tren. Chung ta d§ bi€t muon xac dinh duoc rna tr~ he sA [K] cua h6n hop gAm n chAtthi ta phai sir dung t6i thieu n dung djch han hop chuan va do tai tbi thieu la n biroc song .lC1 the giam sai s6 trong phan tich chuftn bang each ap dung nguyen "su dung sa /U(Y11g dung cac dich h6n hap chudn nhiJu han K2._4~g_q~f!_.[A] . khi do m6i I§n chung ta chi can dung gia tri phan tich cua n dung dich chuan trong s6 p dung dich sir dung (p en = P p > n). Vi d\1: vfut voi tnrong hop han hop co 2 chAt 6' tren. .cu the nhtr sau: Tai biroc song I dung djch han hop chuan 1: Al Tai buoc song 2 dung dich h6n hop chuan 1: A3 = K2. de giai loai h~ nay ta dua v~ viec giai h~ Cremer.lC3 + + K1.2C4 = Kl. tY Ie K.IC1 + K2. V~ nguyen lAc. co nghia la ta dd phai giai 10 he co 4 phuong trinh d~ xac dinh 4 An s6 la cac h~ s6 tY Ie K cua 2 chAt tai hai buoc song.overdetermined system". d~ phan tich chuan chung ta se dung 5 ChUM hon hop. mai he c: 5= 10 tnrong hop va se co 10 gift tri rna tr~ chuan hoa K._?__!. Til cac gift tri K nay. nghia la ta se co nrong ung en h~ Cremer va e. tinh duQ'c rna tr~ trung binh [K]tb va se xac dinh duoc nong dQ cua m6i thrum ph§n trong dung dich chuan h6n hop theo cong thirc: [C] = [K]tb-1. (rn = n = p) de co n2 phuong trinh xac dinh rn9t nghiem duy nhAt cua h~ gAm n2 phcln tir cua K. m6i nghiem gAm n2 gia tri nrong img voi n2 phcln tir cua he sf> T ~ . en tnrong hop. Vi du: muon xac dinh cac h~ s6 K cua h6n hQP gAm 2 chAt.1C3 + KI.!_!~~_~~~l}_ Gilt thh~t s6 hreng cac h6n hop chuan duoc sir dung Ia p. ta co ly binh phirong tbi thieu = K2.2C2 dung dich han hop chuan 2: A2 = Kl.2C2 dung dich h6n hop chudn 2: ~ Tren tlnrc t€. khi do he tren se tro thanh ~~he tren xac dinh. ta phai sir dung tbi thieu 2 dung dich h6n hop chudn va do rn~t d9 quang tai t6i thieu 2 buoc song khi do ta se co 2 x 2 = 4 phuong trinh xac dinh cac gia tri cua h~ s6 tY Ie Km.

2u Irong phlin tich Sau khi phan tich chuan d~ xac dinh rna tr~ h~ sa tY l~ [Kltb va chAt hrong cua no dira vao cac thong ke da: neu. detector chu6i diot dUQ'cnbi voi bQ truyen va bien dc3idft li~u tac di) eao. Sau do. rna ta pha ban dAu cho m6i thanh phAn trong h6n hop ta se tinh duqc S\l' sai khac gitra nAng de. cuai cung la xir Iy k~t qua dua vao phArrmem tren may tinh di~n nr._7. trong tnrong hop dung 6 bmrc 2 C6 = -" song pharr tich cho hon hop gem c6 hai chat.. Nam 1989-1990: Hang Beckman gioi thieu phAn mem pharr tich quang ph6 MCA tren cac may quang ph6 Beckman DU thong thuong. Phlin tich mflu Ihir va ap dung Ihu{il loan hinh phu01Ig mduthir a tren va nAng dQ thirc cua cac dung dich chuAn h6n hop.:l!__. ta co th~ dung cac thong ke nrong quan ta._ _. b. rna tr~ [Kltb duoc sir dung d~ tinh true ti~p nAng de. ta lai g~p bai toan t6 hop ch~p n cua m phfut tiro Vfut a vi du tren. Cac th~ he may quang ph6 hien d~i sau nay nhu: DU 650i. d~ tinh n6ng dQ chua bi~t cua miu thir. khi tang sa buoc song pharr tich se giam duqc sai sa cua phep do (giam gia tri t&ng binh phtrong cua su sai khac gitra n6ng dQ trung binh va n6ng di) cua nrng tnrong hop t& hop biroc song). tnroc h~t chung ta phai lua chon mi)t sa buoc song pharr tich thich hop dai voi m6i thanh phArr. _ So sanh cac gia tri C nay voi gia tri nAng de. cac may diroc trang bi bi) vi xir Iy tac di) cao. HP8453 cua hang HP e6 su cai tien ro ret ca v~ phAn cirng va phArr mem. va da: c6 thS thuc hien diroc ngay tit khi co may quang ph& UV -Vis. do han ch~ v~ di) ehinh xac cua cac thi~t bi phan tich. cho phep phan tich ph6 nhanh hon. chua bi~t cua miu thir. va sai sa se cang nho khi sa bircc song pharr tich cang tang.!_!~~_~~~1}_ . chung ta se dung sa hrong cac buoc song phan tich Ian hon sa cAu tir trong h6n hop (m > n) bang each sir dung them nhieu thong tin hon cua ph&. tang di) nhay va di) l~p lai cua biroc song. tinh diroc d~ danh gia sai sa cling nhu chAt hrong dtrong chuan .. VS phan cirng. D~ phan tich MCA tren the h~ may nay. chung ta se giai duoc tinh duoc. Ph6n mJm cho phdn tich da ctiu tu MeA 15 gia tri cho n6ng dQ cua m6i thanh phAn va k~t qua se la gia tri trung binh cua IS gia tri rna ta Th\I'Cte. d~ giam sai sa efta phep do. Tuy nhien. Theo nguyen Iy binh phuong tai thieu. cilng nhu han ch~ v~ thi~t bi xir Iy sa li~u d§n d~n ket qua phan tich khong chinh xac hoac co k~t qua. _. m6i IAnta chi cAn sir dung gia tri di) hAp thu quang do tai n buoc song trong sa m biroc s6ng pharr tich._4!!g_!l!. DU 7000 cua hang Beekman hay HP8452._. Nhu v~y. cAu hinh quang hoc cai ti~n. co sa Iy thuyet cua phuong phap pharr tich da cAu til (MCA) cling nhu cac thuat toan d~ giai quyet no da: eo tic lau. Ih. Do do.16- the do duqc chinh xac nhung lai phai kha cong phu trong viec tinh toan . . •:. sau do tien hanh phan tich cac miu chufut va miu tlnr.·_ _!.

_~·__4!!g_q~q_. dit li~u ph6 trong khoang biroc song da chon dung cho phan tich. Thic§tl~p cac thong s6 chung . r d6ng thoi thu diroc toan be. t6 hQP de tren xac djnh-overdetermined) xu ly k~t qua cho phep ap dung ky thuat MCA de phan tich duoc mQt s6 chc§pham c6 ill 2 d~n 3 thanh phfuJ. Su cai ti~n ve giao di~n phfut mem.!_!~~_~~f. xu ly du li~u ph6~ cling nhir Ia ap dung cac thong viec tinh tom k~t qua tra nen dan sa kiem ke toan hoc da lam cho gian han voi sai s6 t6i thieu. dung thuat toan chuyen h6a chu6i Fourier trong Hien nay . Hinh 5.17- . a nhieu co nghiem chua dugc trang b] cac th~ h~ may quang phA hien dai nhu tren. vi v~y chung toi da thi~t l~p mQt phdn mem hApthu quang tren may quang ph6 thong thuong. Hinh 4. Chuang trinh h~ plurong trinh Cramer.'!':. xu Iy nay rna thuat giai h~ Cramer (h~ cua n6 dua tren viec giai quyet hai bai toan chu y~u~do la: plnrong phap Gauss de khir xu ly cac kc§tqua thu duQ'c til nhieu cung voi viec loai be cac kc§tqua qua sai l~ch theo nguyen ly cua thuat binh phuong t6i thieu (least square method). Cira s6 chuang trinh phan tich da cAu til MCA.

. 3. Thu6c co 5 thanh phdn: + Paracetamol._. + Paracetamol va ibuprofen. khao sat tinh tuyen tinh. clorphenirramin maleat va phenylpropanolamin hydroclorid.!g!!~~!! _ c:_0!_ . bromhexin hydroclorid va clorphenirramin maleat... cu th~ nhu sau: Thuoc co 2 thanh phan: + + Paracetamol va cafein.!l9l cho cac ti€u d~ tai.:.18 - . Nghien ciru phirong phap xu Iy mdu. chirng minh bing thuc nghiem tinh dung. Thir nghiem tim kiem ky thuat hoac giai phap d~ loai trir anh huang cua cac thanh phfut khac (k~ cft ta duoc).2. NQi dung nghien ciru: . Chon min. •:. M6i tieu d~ tai chon t6i thi€u la 2 mdu thuoc d~ nghien ciru voi lam cac khao sat thuc nghiem.}_. + Paracetamol va acid mefenamic.. •:. co tir hai thanh phan tra. s6 hrong dli d€ lJtJi tlf(1llg nghien cau Cac mau thuoc ap dung tuy theo thi tnrong cung c~p. Mfii chuong trinh cho mQt cong tlnre thn8c se Ii mQt ti~n d~ tili. DOl TUONG vA PHUONG PHA!> NGHIEN CUU 3. tinh chinh xac. . + Theophyllin. ephedrin hydroclorid va phenobarbital. Danh gia ich lei va tinh kha thi cua phirong phap . cafein. D\1 kien xay dung phuong phap dinh tinh va dinh luong mQt s6 thuoc co chua tir 2 d~n 5 thanh phdn.__. pseudoephedrin hydroclorid. .. khai thac cac irng dung cua phuong phap s~c ky long hieu nang cao (HPLC) va phirong phap quang phi. U ng dung cac phirong phap da xiiy dung vao viec kiem nghiem mQt s6 thuoc dang hru hanh tren thi tnrong. Thi~t k~ nghien ctru f)~ tili (hrgc thi~t k~ theo mo hinh nghien cnu thvc nghi~m t~li pheng thi nghiem. 3. crr min Chpn mau va cO mau va dBi ttrQ'Dgnghien ctru Chon cac m~u thudc di€n hinh.1._ P_~U_l[_(!!l_g_ _v_~ l!!!'!l!!!g p_~_qp__. Paracetamol va quinin sulfat. Thu6c co 3 thanh phan: + Paracetamol. Nghien ciru xay dung cac phirong phap dinh tinh va dinh hrong d6ng thai nhieu hoat chAttren cac thi~t bi HPLC va quang ph6 UV -Vis hien co .. •:. UV -Vis hien dai van viec phan tich cac thuoc da chon . •:.

19 - . tY l~ cac thanh phfut cua pha dt)ng._~·__!_~U'!_f{!!g__':~l!!?'!_'!!}gp_~_4P__1Jg!?!~!!E~ f 3.1. detector) . kich thtroc cQt ra sao. detector hong ngoai (IR) . Phuong phdp xac dinh cac chi lieu nghien cuu . d~c biet lit co kha nang quet ph6 va do nhieu buoc song cung mt)t luc. detector ion hoa ngon hra. em." n~u hi rna giai ding + Thanh phan va chuang trinh dung moi n~u lei rna giai gradient. detector detector do do wavelength wavelength a a .3. .. 3. detector huynh quang (FLD: fluorescence co th€ g~p mQt s6 loai detector detector chiet suat vi sai. Ph6 bien nhAt lit detector UV.900nm) nhir: detector mang diode nhieu song bUGC song thay dbi (MWD: multi (VWD: variable buoc Trong do detector mang diode hi loai detector hi~n d~i co dt) nhay rAt cao. Pha dt)ng: + Thanh phan va dong (isocratic).3. detector hftp thu tir ngoai (UV).Vis). <IQ xfip hat . Phuong phap nghien a. detector). Chi lieu nghien cuu Cac chi tieu nghien ciru duoc mo ta 6 sa db sau. LU'a chon di2u kien sac kV Thit~t bi HPLC V6i may HPLC ta quan tarn nhat toi detector. cO"hat.. sau: detector hdp thu tir ngoai . . detector).Vis (l90nm (DAD: diode array detector). cac thong s6 v€ Ioai pha tinh. PhU'01lgphap siic kj long hi?u nang cao (HPLC) b.kha kien (UV..:.. do do d6i voi mot h6n hQP gbm nhieu thanh phfut ta co th€ chon cho m6i thanh phan mt)t bu6c song ph at hien thich hQP nhftt... Loai ct)t dung phan tich (pha tinh): cQt cua hang nao. pH .

theo cac duoc di~n hoac sai s6 nrong d6i). thay d6i •:. Ti~n hanh pha mt)t dung dich g6c..20- . nong de>cua m6i chftt phan tich deu co m6i quan h~ tuyen tinh voi dien tich hay chieu cao pic sitc kY (trong mQt khoang n6ng dQ nhdt dinh nao do). Do do. . Tien hanh khao sat d(> l~p lai bfing each dinh hrong rieng biet tren nhi~u mau gi6ng nhau ella chat can phan tich r6i xu Iy ket qua bang phirong phap thong ke. neu cac pic tach khoi nhau hoan toan. Nghia la trong khoang n6ng d(> do thi dien tich (S) hay chieu cao (h) pic phu thuoc vao nbng d(>(C) theo mt)t ham b?c nhdt. Khao sat do chinh xtic CUD phU01lg phap Be> chfnh xac tlnrong duoc xac dinh thong qua d(> l~p lai cua phirong phap (each thong thirong nhdt Hi xac dinh d(> lech chuan nrong dbi cua k~t qua phan tich RSD .. pic nho._ p~~ L _~l!_f!!!g__~~ p!!l!'!!}g_p~_qp_ _. thong thtrong ta tinh k~t qua bang each so sanh mau chuan va mftu thir trong cung dieu kien. Slit . daub gia dQ tuyen tinh thong qua h~ sf>nrong quan r . sau do pha loang dung dich g6c nay d~ thu duoc m(>t day dung dich chuan bi~t truce n6ng dt).!g!!~?!!E~ Luu pH . Th~ tich tiem: thtrong la 20Jll. T6c de>dong pha de>ng: khao sat d~ chon t6c d(>phil hop nhat. Khao sat tinh thich h{!JJclio he thAng Yeu cftu a buoc nay co thich hop khong? la phai kiem tra xem cac di~u kien site ky ta da lua chon Ta thtr chay me>t mftu phan tich vai dieu kien sitc ky da chon.C + b hoac h = a. ta dich chuan va cac dung dich thir cho qua trinh sitc ky . •:. gon la duoc . b la h~ s6). din chuAn hi cac dung •:. l?p phirong trinh h6i qui. Nhi~t dQ c(>tphan tich . Bmrc song phil! hien: phai thich hop voi m6i thanh phftn. y: Pha d(>ng la m(>t y~u t6 rAt linh d(>ng. Chu8n hi cae dung dich phlin tich Trong phtrong phap HPLC. •:. S = a.C + b (a. . Bern cac dung dich chuan nay chay s~c kY d~ thu duoc gia tri dien tich hay chien cao pic. 50Jll. ta co th€ d€ dang thay d6i dS thu dtrcc k~t qua tach t6t nhAt bang each thay d6i tY l~ cac thanh phan. Khao do turin tinh CUD cae thimh phOn can phlin tich Ta bi~t rang. Chung ta can phai xac dinh khoang tuyen tinh nay bang thirc nghiem tir do lam co sa d~ pha cac dung djch phan tich co n6ng dt) nam trong khoang tim diroc.

:.:.:. Phon Ilch mau thu . KhaO sat phA hAp t11\1 UV va IvachQn elk btr6c song.21 - . Phuong phap quang phD phon tick da cdu tIC(MCA) a.:. xac dinh phan tram tim lai.2._~ . Xac dinh khoang nang do phon tlch .!g~!?~_ ! t. Khao sal do dung cua phuO'ng phap _ __ - 0 De> dung duoc xac dinh thong qua kha nang thu hbi cua k~t qua phan tich khi dung phirong phap them chuan. trong khoang tuyen tinh da khao 3. Xoy dU'ng. hoac gil'. Danh gia do dung va do chinh xac cua phuO'ng phap Phdn nay tuong 1\1 nhu d6i voi phirong phap HPLC. tai uu duirng chunn hdng phOn m2m tTen may tlnh . danh gia. Phuong phdp xac dinh cac chi lieu nghien cUu va Iua . [hoac giai song phan tich. Do dO hap thu quang cua cac dung dich chuan han hem .}. song phon b. __}_~Ul!'_f!!1:g_ _~~ p!!'!_(!!!Z p_~!P__. Chuan hi day dung dich chunn hDn h(!fJ .3. Khao sat Dhb hap thu UV tlch a sa db sau. Them vao mdu thir met hrong ehinh xac ehdt chuan da bi~t tnroc ham hrong sao eho dung dich eu6i cling co nbng d{>nk sat.:. 0 ] J CcO ] ) .:. chon cac huuc song.:.:. Chi lieu nghien ctru Cac chi tieu nghien ciru duoc mo til .

thuat binh phirong t6i thieu d~ danh gia Cac 49c trung th8ng k2 re xu Ij kit qua phiin tich: x:.:. Phuong phap xir - . _ Iy s6 Ii~u h6 tro lit chuong trinh Microsoft Excel. str dung cong cu chuan va thir. Danh gia phirong phap phan tich va cac k~t qua phan tich: sir dung phuong phap thong ke.:.!gp~_qp:_ng~~~!!_. Str dung phuong phap h6i qui tuyen tinh.~ i i-I + DQ lech chuan (standard deviation): + Sai s6 chuan: + DQ lech chuan tuong d6i (relative standard devitation): n -1 RSD (%) = ~ x 100 x ._ _f!~U'!_(!:!g_l!~l!!!~.22- .!?."'x n 1 + Gia tri Trung binh: n .!_~ L 3.4.

~0. detector UV va chuang trinh sAc ky d~ng dong.1:.:t.28%) va 21.2. q'!_q.__ . d~ nguoi. hoa chat a. 5 urn).. bromhexin pseudoephedrin hydroclorid. A. _ va djnh hr4]llg paracetamol. . Hod chdt dung moi Methanol tinh khiet site kyo Dung dich d~m Amoni nitrat pH 9.1.5 (884 ml mroc cho them 94 rnl Amoniac d~m d~e (25 .. .23 - . . .45 urn.VIS.' .5 ml acid nitric (69 .5 bang acid nitric hoac Amoniac. Vi v~y de giup cac co s6 xay dung tieu chuan cho san pham cua minh.71%). . giam dau. chua ho "Cotussin" do cong ty diroc pham Tien Giang nghien diu san xudt c6 cong thirc nhu sau: Paracetamol (PA) Cafein (CA) Pseudoephedrin hydroc1orid (PE) Bromhexin hydroc1orid (BH) Clorpheniramin maleat (CM) 280 mg 30 10 8 4 mg mg mg mg Trong cac Uti lieu tham khao. . b. hydroclorid. f)i~u chinh pH d€n 9.1 mg. !!&~!?_'}. clorpheniramin phap HPLC maleat va cafein bing phuong Vien nang ha nhiet. - Dung moi A: h6n hop Methanol: Nuoc (1 : 1). Ce>tLichrosorb Si 60 (250 x 4 mm. chua thdy san pham nao c6 cong thirc nhu tren. dung miJi. Can phan tich voi de>chinh xac 0.c nghi~m A. Dieu kien sac leY . 4.May sac ky long hieu nang cao HP 1100 .. May lite sieu am. .'. Th. May moe. chung toi dl1 nghien CUu phirong phap dinh hrong 5 hoat chdt tren trong vien h6n hop bang phuong phap HPLC voi di~u kien sitc ky long pha thuan. Phu01Jg phap a. KET QUA NGHI"EN CUu 4. khuay d~u.. E¢!. May moe dung C{l May site ky long hieu nang cao HP 1100 voi detector UV . . A. LQc qua mang loc 0. Djnh tinh .1.Hewlett Packard. .

. 10ml NaOH IN. PE..45 urn ._. ~::::l .______ .. BH va CM: Tron d~u va nghien min hrong bQt vien lfiy tir 20 nang..... l~c d~u.. ~ aUG . l~c d~u.. them pha dQng toi vach. Dung dich dem Amoninitrat - Th€ tich tiem: 20 ul.45Jlm. Can chinh xac mQt hrong bQt vien nrong irng voi 2 vien. b6c hoi tren each thuy d~n h~t Hoa tan c~n trong 20mI dung dich HCI 0. PE. Dung dich chuan d€ dinh hrong CA. them pha dQng d~n vach.. _ T CQt Lichrosorb 4mm. •:.. Si 60 (250 X .. IN rbi them methanol vira du 200mI.. khuay cho tan h~t rbi xir Iy ti~p nhu mau thir.. 298 nm do CA va BH.lglml. 15mI pha dQng.. l~c ky rbi chiet bang 3 IAn x 30ml.. l~c khoang 10 phut.. Dung dich thir - sdc kY Dung dich thu dS dinh luong PA: Can chinh xac mQt hrong bQt vien tucmg irng voi 30mg PAvao binh 50ml. Dung dich chufut Dung dich chuan d€ dinh hrong PA: Pha chfit chuan PA trong dung moi pha dong d€ thu ducc dung dich PA co nong dQ chinh xac khoang 30J. _. uie khoang 10 phut.5 (45 : 6) Detector UV . ._.. pH 9. IQc qua gifiy IQc thuong. GQP dich chiet.. LQc qua gifiy IQc thuong.._ . Kit - nehien cUu . ..VIS: 257 nm do PE va CM.. . 20mg PE. _0': _. cho vao mot c6c co mo. them 30 ml pha dQng. 10mI dung dich BH. . Pha dong: MethanolT6c dQ dong: 1. Dung 30 mi mroc d€ chuyen h6n hop nay vao binh gan.. " Tinh k~t qua: Dtra vao dien tich hoac chieu cao cua pic chuan va tlnr tirong (mg. 1... them 30ml pha dQng. sau do IQc qua mang IQc 0.... . hoa tan trong pha dQng vira du 25ml (dung dich BH) + Can chinh xac khoang 560mg PA. 1..24- .. b. CM va BH: + Can chinh xac khoang (dung dich CM) 40mg CM. 4. 5 urn). .. sau do IQc qua mang loc 0.. them chinh xac 5mI dung dich CM. 60mg CA.:.0 ml/phut do PA. Dung dich thir dS dinh hrong CA.. hoa tan trong pha dQng vita du 25ml + Can chinh xac khoang 40mg BH. PA. l~c d~u. __ .0 ml/phut do CA va BH. Hut 2ml dung dich tren cho vao binh dinh mire 20ml.5 ml/phut do PE va CM. Cdc dung dich Hem . Them Cloroform Cloroform. tir doan " dung 30mi mroc d€ chuyen h~t h6n hop nay vao binh gan ..

_ .25 - nfra..•..9985 . trong khoang n6ng dQ da: khao sat..88 = 17.. Khii nang chiit hit hO{ltchat Trong phirong phap xu Cloroform thi chi~t them 1 ly m§u. CM: 5._ _ 4.-.9985 Khoang tuyen tinh dff khao sat (ug/ml) 80 ..--_~.1. PE va CM nhu hinh 1.9998 0.82 B. 40··: . giai doan chiet cac hoat chAt d. co su nrong quan tuyen tinh gitra gia tri dien tich pic va nong dQ (r = 0. h6n hQ'PCA va BH.24x . . __ _ • . 5 .. waveJengffi=25Tnm\THANH\UU9. Bang 1.120 = 2.24 = 0. .27..9. ~ ~ U) 80· ~ <ri 1 .n V6i chirong trinh s~c ky da:neu.• ~-~r-'--~~~~--.5 phut.9999 0.125 20 . 201 10·t i "' .n do va loai be Paracetamol dll ducc khao sat kha nang chiet h~t bing each: sau khi chiet 3x40ml Ian 40ml Cloroform . .0..300 25 .9999 0. PE va CM voi cac nong dQ khac nhau.~~.30x . . -" . S~C ky d6 cua CA va BH Hinh1. S~c Icy d6 cua PE va CM PE : 4. L B. N6ng d9 dung dich chuan va dung dich thir cua chung toi nam trong khoang tuyen tinh dll khao sat.. Cac ket qua tren cho thay.1.._-- ) 5 10 rniFl Hinh 1.7.9987 0.99x + 20.400 20 . Ket qua diroc gioi thieu a bang I . s~c ky d6 da:tach cac chat CA va BH.3 phut B. .---~--~'---..6x + 118._ .88 = PE BH PA 11.1.11 = 15. . Khiio sat khoiing tuyJn tinh Chung t6i da:khao sat su phu thuoc tuyen tinh gitra n6ng dQ cac hoat chat va dien tich pic tren 5 dung dich chuan cua PA.--... J . mAU 120 .1 va hinh 1. Kh q_ua nghien cuu _ _ _ _ _ _ _ _ _ __ ...1.. C --..8 phut BH: 4. .'--vwm'A.. K~t qua va bifn lu.2.120 60 .. ..6 phut.2.2. CA: 6.__rnf[) {I ...1'0 . 40 .9999).. Ket qua khao sat d9 tuyen tinh Thanhphk CA CM Phuong trinh h6i quy y y y y y H~ s6tuong quan 0..57x .. _ . L6p Cloroform chi~t l~n 4 nay .

Dp I~p l(1i.~ ' . K~t qua khao sat dQ l~p lai va dQ dung tren mftu COTUSSIN sA li~u thAng ke PA 278.85 98. Kha nang chi~t duoc dam bao. sai sa va dp dung Cac thir nghiem nay ducc thirc hien tren mfiu vien Cotussin cua cong ty Diroc phAm Ti~n Giang.23 99.08 0.2. Bang 1. hoat chdt dll dircc chi~t h~t 6 3 IAn dAu.26 0.21 0.1 Thanh phan CM PE 4. hoa tan cin trong 5ml dung dich HCI O. hrong chuan them vito 20% m6i chat) CA 29.~~4!.38 1. SKS: 071199.~ ~ "~" ~.31 99. Nhir v~y.38 9. B. .5 99.q'!_q~ ~~ . ~~ ~g_~!~'}~ ~~~~ ~ " . rbi do HPLC theo chU011g trinh tren.05 0.4 • 99.0 GiA tri trung binh X ( mg I vien ) DC) l~ch chuan S DQ l~ch chuan nrong d6i Ty l~ tim l{lidiroc ( %) ( n = 3.4 0.83 1.4 K~t qua khao sat cho th§y dQ l~ch chuan nrong d6i tuy thea nrng tnrong hop tir 0.1%.3.0 BH 7.2. K~t qua thir tren 3 binh d~u khong xUdt hien pic tren s~c ky db.23 .~~·.2.15 2.63 0.07 98.. K~t qua diroc gioi thieu trong bang 1. ducc b6c hoi tren each thuy d~n kho.07% va tY l~ tim lai diroc hoat chdt tir 98.17 1.lN them Methanol vim du 20ml.

.. 1011m). Kit ~. nghien thanh be)t min va tron deu.. Binh hrong dAng thm Paracetamol (PA) va Acid mefenamic (AM) trong vien nen bao phim Pamesic bing phmmg phap HPLC Vien bao Pamesic do cong ty v~t tir Yt~ Ti~n Giang nghien ciru san xuit co thanh phan nhir sau: Paracetamol (PA) Acid mefenamic (AM) 500mg. Thi~thi.] chua co chuyen luan v~ hai thanh phan nay. nehien cuu . 4...ng dung moi pha dong d€ diroc dung dich chuan co n6ng dQ cua PA khoang 80 ug/ml va cua AM khoang 40 ug/rnl. h. Hai chit tren co de) tan nhir nhau (d~u d6 tan trong kiem) nen rftt kho chiet tach. fJiJu kien sac IcY - CQt Lichrosorb RPI8 (250x4 mm. _ .... _ .I.2 bang acid phosphoric... Trong cac diroc dien hien hanh [19. ._. Phuong ph tip nghien cau a.. 23.... .2... Pha dong: Acetonitril ...2.tetrahydrofuran (3 : 8 :9) dieu chinh d€n pH 2. . sau do pha loang ba. Vi v~y chung toi da:nghien CUu phuong phap dinh tinh va dinh IUQ11g 6ng d thai eel2 thanh phan tren trong h6n hop thuoc voi muc dich cling co chuan cho san pham maio A. hoa tan bang 5 ml THF.... Chu{m bi dung dich - Dung dich thir: Can 20 vien.. Be) IQcdung moi va IQCmftu voi duong kinh 16mang IQc 0. . Dung dich chuan: Can chinh xac khoang 0. Can chinh xac met luong bOt vien nrong (rug voi kh6i IUQ'l1g .. Chftt chuan paracetamol va acid mefenamic do Vi~n Ki€m nghiem . Th\l'c nghifm A. hod chtit May sAcky long hieu nang cao HP 1100 voi detector UV -Vis." _.45 11m.... tetrahydrofuran loai dung cho HPLC. T6c d9 dong 1 ml/phut... .1 g chdt chuan PA va khoang 0.05 g chit chuan AM. 27..27- ...BQ Y t€ cung cap. .. 10Ilm). . nUG ::t _. .. - - .. Th€ tich tiem 20111...._ ... tinh kh6i IUQ11g trung binh vien... 29.... . 250mg. 4. Detector UV d~t a buoc song 279 nm.. .. _0_ . .. sa xay dung tieu A. N- . Acetonitril. _ .. - _.. Acid phosphoric tinh khi€t phan tich. _ . C9t Lichrosorb RP18 (250x4 mm.mroc .

k~t qua khao sat de) a bang sau: Bang 2..ffi.8 3098....6 1883. _ __ . Chuan bi me)t day dung dich h6n hop chuan trong pha de)ng tuyen tinh diroc trinh bay co nong de) cua PA bi~n Thien trong khoang 20 - 200 ug/rnl va cua AM bien thien trong khoang 10 .... -_ .9996 .9 3 4 5 Khoang nong d<) tuyen tinh d1lkhao sat Phuong trinh hoi quy H~ so nrong quan = 19...35 x + 20..1. - -- - ......07 .... K~t qua B. - _ .. Or __ .. LQc qua mang IQc 0. Ket qua khao sat de>tuyen tinh STT 1 2 PA Nang d<) (ug/ml) 20 40 80 160 200 20 -7 200 Y Dien tich pic 401. Khiio sat khoang tuy2n tfnh Chung t6i ti~n hanh khao sat de>tuyen tinh gitra neng dQ cac chat d...100 ug/ml.4 AM Nang d<) (ug/ml) 10 20 40 80 100 16 -7 80 Y Dien tfch pic 456. - _ ..... B.6 803...65 x .. hoa tan bang 5 ml THF.. - - -_ .1..3 4711...451J. s~c ky db thu diroc PA va AM diroc phan tach hoan toano a hinh 2... S~c kY db thu duoc cua dung dich hem hop PA va AM B. Khao sat tinh thich h{1JJ cua h? thang sAc kj V6i di€u kien s~c ky du chon nhtr tren.4..__________ 4. - - - - _ ..1 938.28 - = 46...5 3901. cua khoang 50 mg AM.6 1568.n dinh hrong voi dien tich pic tuong irng tren cac chftt chuan PA va AM. ---...9999 R=0.l..26 R =0.1.1 cho thay mAU N 160 140 120 100 80 60 40 20 o~----~~--------~--~--~ Hinh 2... pha loang bang dung moi pha d¢ng d~ duoc dung dich thir co nong de>cua PA khoang 80 ug/ml va cua AM khoang 40 ug/ml lac d€u. - -- - - - _ . _ ..1 3650. Kit :::l nehien cuu aua 0 ~ .

. Db thi bieu di~n S\l phu thuoc tuyen Hinh 2. K~t qua khao sat dQ l~p lai tren miu vien nen bao phim Pamesie MJu 1 SKS: 011102 SIT 1 2 3 4 5 6 PA AM So lieu thong ke Ham hrong (mg/vien) 511.32 505.21 RSD%=0.55 S = 1. - - • - - • - - ---- - -+ ~+- - - -- - --- . - - --- --.49% - S =4.75 248.15 499.n xet: Trong khoang nbng de>da khao sat co SI! nrong quan tuyen tinh gifra dien tich pic va n6ng dQ voi h~ s6 nrong quan r~t gful 1 (r = 0.3. Kit qua ng_hien cuu .3..75 248.83% .97 So lieu thong ke X .= 506.29- . __ _ ~ T ~ _ r L L-+~ -+_ - - --.08 X = 248.2a.0. Chung t6i chon n6ng dQ dung dich thir va chuan d~ dinh IUQ'Ilg nim trong khoang tuyen tinh da khao sat (PA khoang 80 ug/ml va AM khoang 40 ug/ml). ----.95 504.79 508.22 RSD%=O.. Paracetamol Acid mephenamic 4500 4000 3500 3000 2500 2000 1500 1000 500 0 0 50 100 150 200 250 2000 1000 0 0 50 100 150 I 5000 4000 3000 Hinh 2.50 250.83 Ham hrong (mg/vien) 247..46 506..54 247. K~t qua khao sat de>l~p hili diroc trinh bay (] bang sau: Bang 2. Db thi bi€u di~n su phu thuQC tuyen tinh nAng dQ va dien tich pie wang irng cua PA tinh nAng dQ va dien tich pie nrong irng cua AM Nh.2. B.9996 .78 247.____ 4.~ . Khao sat 49 /(ip /{li cua phuang phdp DQ l~p lai cua phuong phap diroc ti~n hanh tren hai miu thir vien nen bao phim Pamesie.9999).

30 501.08 (mg/vien) So li~u thong ke X = 495..32 20..99 9.75 RSD%= 1.9% Luqngthem vito (mg) Luong tim thay (mg) 9.88 S = 6.4.13 487.02 252.99 TB Nhin xet: PhU01lg phap co de>dung cao vei kha nang tim lai cua PA la 98.-----------------------.7 98.46 RSD%=0. Bang 2.-_.8 98. .2h.61 X = 252.68 253.76 9.n xtt: Ket qua tren cho thAy phirong phap co dQ l~p lai cao v6i dQ l~ch chuan tuong d6i khoang tir 0.09 19.021202 PA SIT 1 2 3 4 5 6 AM (mg/vien) So lieu thong ke Ham luong 498. Ket qua khao sat de>dung ducc trinh bay iJ bang sau : ham hrong m9t luong chinh xac chAt chudn tuong img v6i khoang 20% hrong co trong miu Bang 2.36%_ B..7 97.77 9.71 Ham hrong 255. Khdo sat 49 dung Khao sat dQ dung bang phuong phap them.~~_i_~'!.49 .31 250. Ket qua khao sat dQl~p lai tren miu vien nen bao phim Pamesic Mau 2 SKS.25 % tim lai 98.2%.97 20..3. Ket qua khao sat dQ dung PA AM SIT Luong them vito (mg) Luong tim thay (mg) 20.3 99.07 503.9 98.32 20.------------------------.1.99 9.9 98.63 252.58% Nb.32 9. them vao miu thir da: hiet wac thir.:t__i~~~~q _<:~ --------------------------_.30- .21 495.9% va cua AM la 98. ----------------l __ '!.88 %timl~ 97.2% 1 2 3 20.55 253.36% S = 1.25 488.

CQt Lichrosorb RPI8 (250x4 mm.75% trong h6n hop dung moi methanol .. ChAt chuan paracetamol va cafein do Vi~n Kiem nghiem cung cftp.. Pha dong: Dung dich acid phosphoric 0.\t6 buoc song 273 nm. vi du vien Pasepan cua CTDF Ha Tay hay vien Sedapa ella XNDFTW 2.. tinh kh6i hrong trung binh vien. 4. hoa tan va them dung moi A d~n vira du 100 ml. h.16]. A. Chudn hi dung dich Dung dich chuan: Chuan bi mQt dung dich h6n hop chuan trong dung m6i A co nong dQ cua PA khoang 600 ug/rnl va cua CA khoang 20 ug/ml.I. T6c dQ dong 1 ml/phut. DiJu kien sac Icy CQt Lichrosorb RP18 (250x4 mm.3. Thuc nghi~m A.mroc (1:1). Detector UV di.45f. 10f-Lm). thiit - de m~c sai s6. moi va hoa chat. Can chinh xac mot hrong bQt vien urong img voi kh6i hrong cua khoang 60 mg PA.cUu 0 . . Hoti chiit. dung bi May s~c kY long hieu nang cao HP 1100 voi detector UV. Dung dich thir: Can 20 vien. Phuong phap nay co nhiroc di~m la phai qua biroc chiet tach kha phirc tap. IQc qua giAy IQcthirongfbo khoang 20 ml dich IQc d§u). acid phosphoric (PA). __ __ __ . lOf-Lm).2. Phuong phtip nghien cuu a.31 - -- ? . The tich tiem 20f. Sau do IQc qua mang IQc 0. 16 mang IQc 0. Ethanol tuyet d6i (PA). __ __ __ _ . De dinh tinh va dinh hrong cac hoat chat trong h6n hop thuoc tren thirong ap dung theo tieu chan cc sa (chiet tach r6i do quang) [2. Be>IQc dung moi va IQcmftu voi dtrong kinh Methanol loai dung cho HPLC. nghien thanh bQt min va trQn deu.45 urn. Binb hrqng dAng tbm paracetamol phAn bing phmrng phap HPLC (PA) va cafein (CA) trong thu6c da thanh Thu6c da thrum phdn bao g6m paracetamol va cafein la mot dang ph6i hop thong dung. t6n nhieu thai gian.1m. Kit qua nehien .11. Chung t6i dff nghien ciru mQt chuang trinh HPLC dan gian va tach t6t han chuang trinh dff de c~p trong cac tai lieu tham khao [29] de dinh tinh va dinh hrong d6ng thai 2 thanh phdn tren. Dung moi A: Ethanol._ _ _ _ _ .. _____ 4./ .mroc (35:65). A.

. 4.........2x + 154. _0 .750 ug/ml va cua CA bi~n thien trong khoang 10 ......._.....-..... nehien ... . ... _ - -<'...9995 -32- .. K~t qua khao sat d9 tuyen tinh STT 1 PA Nang dQ (pg/ml) Nang dQ (~ml) Dien tich pic 2 3 4 5 Khoang 150 300 450 600 750 2370 4701 7094 9412 11423 10 20 30 40 50 10 ~ 50 Y = 46.-.4x + 29...l..3 r= 0. - - - _..J . k~t qua khao sat dt) tuyen tinh duoc trinh bay a bang sau: CA Dien tich pic Bang 3...9996 470 978 1432 1901 2330 nong de> 150 ~ 750 tuyen tinh dff khao sat Phuong trinh hoi quy H~ so tuong quan Y = 15..1....50 ug/ml...-. Kit ...... Kit qua khdo sat d{J tuyin tinh Chung toi tien hanh khao sat dt) tuyen tinh gitra nong dt) cac ch~t cdn dinh hrong voi dien tich pic nrong ung tren cac ch~t chuan PA va CA.__..... K@tqua V6'i di~u kien s~c ky ad chon nhir tren..-.. mob 3. - .._... Sllc ky d6 thu dircc cua dung dich h6n hop PA va CA B...... Chuan bi mot day dung dich h6n hop chuan trong dung moi A co n6ng d9 cua PA bien thien trong khoang 150 .-_ . - - - _ ... cUu ..9 r = 0. B...qua ........1._. . chung toi thu dircc sAcky a6 cho thay PA va CA diroc phan tach hoan toan nhir hinh 3.....

+ Paracetamol T __ - -- - T _- - - -~ _ --- - _ .4. K~t qua khao sat dQ l~p lai tren m§u SEDAPA.83 = 0. ____ •Kit nUG ::t nehien cuu O~ .3.54 RSD%= 0.9 287. vira du 1 vien Ta duoc: Mltu 1 SKS : 350900 Mltu 2 SKS : 361000 Bing 3.66 9.37 Ham 9..64 = 0.9 Ham 9.52 9.3 288.75 .09 RSD% - 9.97 RSD% 6 301.63 9.76 9.36 303. Mdu 2 SKS: 361000 SIT PA CA So li~u thong ke Ham hrong (mg/vien) 301.3.-- - -- .62 X S (mg/vien) S = 1.30 305.83 9. Db thj bi~u di~n S.40 302.92% 9.2.7 286. K~t qua khao sat de>l~p lai tren miu SEDAPA.53% (mg/vien) S = 0. MJu 1 SKS: 350900 SIT PA CA (mg/vien) So li~u thong ke Ham hrong 291.71 9. DQ l~p lai diroc khao sat tren hai miu vien nen SEDAP A do XNDPTW II san xudt c6 thanh phfut: Paracetamol: Cafein: 300 mg.! phu thuQc tuyen Hinh 3.4 X (mg/vien) S = 1.-- _.33 - 9.82 9.1 288.-- - - - -- - - --- - --- - .57 9.51% (mg/vien) - 9.93% Bing 3. 10 mg. --- - ---- Cafein 2500 2000 1500 1000 15000 10000 5000 0 500 0 0 200 400 600 800 0 20 40 60 Hinh 3.86 hrong (mg/vien) So li~u thong ke 1 2 3 4 5 X = 302. Db thj bi~u di~n su phu thuoc tuyen tinh nbng dQ va dien tich pie tirong ling cua PA tinh nbng dQ va di~n tlch pie tuong ling cua CA B.2.81 301.6 287.52 RSD%=0. - - --- - ---- - -- - - --- - - --- - - .44 .09 = 0.2.71 luong (mg/vien) So li~u thong ke 1 2 3 4 5 6 X = 288. Kit qua khao sat i/{j 19P19.

2 98.886 0._.30 0.300 0.4..1 100.595 0.600 0...898 % tim lai 100..90 them Luong tim thay (mg) 0..3 98.30 0. _... B..30 0. phirong phap co dQ dung t6t.0 99.1 20.30 0..0 97.. voi sai s6 nay eho phep ap dung duoc phirong phap tren.2 % Lugng vao (mg) 0... - --- .3 29.4 98._.9 100. ~__.5 98.4 101.5 99.5 % tim lai 100.: ..u SEDAPA..5...0 99.5 99.6 29.__________ 4. MJu 2 SKS : 361000 PA CA Luong tim VaG SIT I 2 3 4 5 6 Lugng them (mg) 20 20 30 30 40 40 thdy (mg) 20.2 % TB K€t qua tren cho thdY phftn tram tim lai cua PA va CA tren hai mfiu dat tir 98.4 va 3. Kit qua nehien.60 0...5..896 0.1 99.60 0. _ -< .34- . Ket qua khao sat dQ dung tren ma..7 97.1 29.__•• ..1 98.60 0._.7 39..4 40..9% STT 1 2 3 4 Luong them VaG 20 20 30 30 40 40 5 6 TB Bang 3. .298 0.7 99.6 30. Mau J SKS : 350900 PA CA Luong tim thdy (mg) 20.... Kit qua khao sat dp dung Khao sat dQ dung tren hai ma.5 % Luong them vao (mg) 0.582 0..u SEDAPA k€t qua diroc trinh bay a bang 3..8 99. a tren bing phuong phap them chuan.3 98.60 0..2 97.. K~t qua khao sat dQ l~p lai a tren eho thdy sai s6 tirong d6i til 0.90 Luong tim thdy (mg) 0.7 99..90 0.1 39. K~t qua khao sat dQ dung tren mdu SEDAP A.54 den 1. .90 0. .1 (mg) %timl~ 101. Bang 3.293 0.._..3.0 98.8 99.305 0.592 0." ..2 19. . - - _.9 d~n 99...7 39.3 97.884 % tim lai 101.07%..8 100. CUll _ 0.5 %.

_ . .. Thi2t - hi. Detector UV d~t a biroc song 224 nm.___ . I urn). Muc tieu cua chung toi la nghien ciru mQt s6 phirong phap dinh hrong danh gia cac plnrong phap eho cac dang thuoc co thanh phan nrong nr. Kit . D6ng thai mong duoc gop ph~ xay dung cac tieu chuan chdt IUQl1g ella nganh cling nhu cua QU6c gia cho cac A.1. Nghien Ctlu dinh hrQ'llg dAng thM paracetamol thu6c da thanh phin bAng phmrng phap HPLC (PA) va ibuprofen (IB) trong MQt trong nhtrng dang thong dung tren thi tnrong hien nay la h6n hop paracetamol va ibuprofen (vi du: vien nen Alaxan cua xi nghiep United Pharma Vi~t nam [II]. hoa tan va them pha dQng d~n vira du 50 ml.35- .1 % (60:40). natri sulfat khan.45Jlm. dung dich NaOH O. Dung dich chuan : Chuan bi mQt dung dich h6n hop ehuAn trong pha dQng co nong dQ ella PA khoang 65 ug/ml va cua IB khoang 40 ug/ml.. ethanol vc''. CQt Lichrosorb RP 18 (250x4 mm. vien nen diSn Vi~t Nam cling paracetamol va nhu cac ducc diSn khac hien nay dSu chua co chuyen lu~n cho dang bao ch€ nay. Th\lc nghi~m A.. C<Y ibuprofen co trong thanh phk mot dang thuoc voi muc dich lam phong phu them va sa hra chon ap dung. - Ch~t chuan paracetamol va ibuprofen do vi~n kiem nghiem cung c~p. Hut chfnh xac 2. ° BQ IQcdung moi va IQcm~u voi dirong kinh 16 mang IQC0. Phllung phap nghiin cuu a. 4. I~c d~u.45 urn. Th~ tich tiem 20Jll. IQc (bo khoang 20 ml dich 19C dfiu). _ __ __ __ __ __ __ -__ -- -- -- - ..__ aua nehien elm __ _. Diroc nr Y t~ Tra Vinh.0 mI.IN va O. DiJu kien - sdc kY CQt Lichrosorb RP 18 (250x4 mm.2. LQc qua mang loc 0. Diethyl ether. __ o~ ..acid phosphoric 0. 4. them pha dong d~n vita du.0 ml dich IQc tren cho vao binh dinh mire 20. Dung dich thir: Can 20 vien.OlN. Pha dong: Acetonitril. T6c dQ dong 1 ml/phut.. nghien thanh bQt min va trQn d~u.4.. vi en nen Pi-Antalvic [5] cua cong ty Diroc v~t MK protamol cua cong ty cb phan Duoc pham Me Kong . 10Jlm). A..A. Can chinh xac mot hrong bQt vien nrong irng voi kh6i hrong b.5 mg PA.). tinh kh6i IUQl1g trung binh vien. Chudn bi dung dich cua khoang 32. hoa chat 655A-12 voi detector UV- May sAc kY long hieu nang cao MERCK-HITACHI Vis 655A-22.

. S~c kY db thu diroc cua dung dich h6n hop PA va IB B._. Khao sat khoang tuyin tinh Chung t6i ti~n hanh khao sat dQ tuyen tinh gitra nAng dQ cac chelt cAn dinh hrong voi dien tich pic nrong irng tren cac chelt chuan PA va IB_ Chuan bi mot day dung dich hem hQ'P chuan trong pha d¢ng co nong dQ cua PA bi~n thien trong khoang 26 . k~t qua khao sat dQ tuyen tinh duoc trinh bay a bang sau: Bang 4."~>".80 ug/ml.1. D6 thi bieu di€n sir phu thuoc tuyen Db thi bieu dien SlJ phu thuoc tuyen tinh n6ng dQ va dien tich pic nrong img ella PA tinh n6ng dQ va di~n tich pic nrong irng cua IS -36- .9999 --. Hinh 4.2.:.0 R = 0..L·>-"'~~~'_..3. K~t qua khao sat dQ tuyen tinh STT PA Nbng dQ (ug/ml) Dien tich pic IB N6ng dQ (ug/ml) Dien tich pic 1 2 3 4 5 Khoang nong dQ tuyen tinh dll khao sat Phuong trinh hoi quy H~so tuong quan -.lx + 199.1.9997 958 1521 2148 2711 3356 Paracetamol 10000 l+J. -------."FiC':"%· Ibuprofen 4000 3000 2000 1000 8000 6000 4000 2000 o o 50 100 150 o o Hinh 4.C)":::i[:'"·'.130 ug/ml va cua IB bien thien trong khoang 16 ._-- 26 52 78 104 130 26 ~ 130 Y = 67.~--- 1970 3628 5475 7168 8922 16 32 48 64 80 16 ~ 80 Y = 37. 20 40 60 80 100 Hinh 4.".l.--_.4x + 343.g~j~'!_ _c:~ B.4 R = 0. K~t qua ------------------------------------ V oi di~u kien s~c ky da chon nhu tren._(l!i!_ q~4_lJ. cluing t6i thu diroc s~c ky db cho thely PA va IB duoc phan tach hoan toano r .

!~~.6 98.50 6.4 98.2.9999).n xet: Trong khoang nAng de)da khao sat co S1.00 4. ay % tim lai 98.9 336. B.6 99.9 S = 1. K~t qua khao sat dQdung PA IB Luc.0.2 % SIT Luc.76 RSD%=0.6 % 4. K~t qua khao sat dQ I~p lai duoc trinh bay iJ bang 4. 8.37- . tim (mg) 3.9 99.98.3 206.2% va 9 ella IB Iii.83.65% B.7 205.90 3.0. K€t qua khao sat de)l~p lai STT PA Ham hrong (rng/vien) 328.5 96. them va mdu thti' da bi~t tnroc ham hrong mQt hrong chinh xac chAt chuan nrong trng voi khoang 20% hreng co trong miu thtr.0 331.9 96.7 331.mg vao (mg) 1 2 3 4 5 Trung 6.3 IB So lieu thong ke Ham hrong (rng/vien) 203.---- ----------------------------------------------------------------'------------.32 6.50 6.95 3.50 6.mg tim (mg) 6.6%.8 97.1' nrong quan tuy~n tinh gitra di~n tich pic va nAng de) voi h~ s6 nrong quan rAtgAn 1 (r = 0.3. - Nb.43 6.65 .2 98.00 4.50 thAy % tim lai them vao (rng) . Bang 4. Khdo sat ap lpp l{li ella phuang phap D<}l~p lai cua phirong phap duoc ti~n hanh tren miu thir la vien nen Alaxan.3 S = 2.87 4. SKS : 003501.--------. Chung toi chon nang de) dung dich thu va chuan d~ dinh hrong n~m trong khoang tuyen tinh da khao sat (PA khoang 65 ug/ml va IB khoang 40 ug/ml). . K~t qua tren cho thAy phuong phap da xay dung co dQ l~p lai cao voi dQ l~ch chuan tuong d6i khoang 0.0 203.8 100. Khao sat t1P aung Khao sat dQ dung bang phuong phap them.98 3.46 97.2.28 6.43 6.00 blnh Nbtn xet: Phuong phap co de>dung cao voi kha nang tim lai cua PA 18.5 98.4 333.83% X =204.00 4.3 So lieu thong ke 1 2 3 4 5 X =332._~·__l!:4!_qlf_4_ ~g~!~.50 6.1 206.34 RSD%=0.00 4. KSt qua khao sat dQchinh xac duqc trinh bay iJ bang sau : Bang 4.2.02 thJ.mg them Lugng Luc.3.9997 .

h§. hod chat May sAc ky long hieu nang cao HP 1100.. Cot Lichrosorb RP 18 (250x4 mm.. Detector UV: 235nm.VTYT Ti~n Giang (Tiphaco).. --- --. Pha dQng: Ll g natriheptansulfonat 4%-diethylamin ti trong 1 lit h6n hop methanol-acid acetic Ie (650: 350: 1). con voi cac ch~ phAm da thanh phan thi tieu chuan cua cac nha san xuAt dira ra rdt khac nhau: Phuong phap quang ph6 hApthu tir ngoai-kha kien. ..----_.38 - . Cac phirong phap nay thtrong phai chiet tach phirc tap._o~ .. Vien nen Antigrip F co cong thirc nhu sau: Quinin suifat Paracetamol Ta diroc vd 30 mg 150 mg 1 vien chi De dinh hrong cac thanh phan nay... 10J.- -------_.---------_--. Dung moi: Ethanol .. A. phuong phap acidbase...VTYT Tra Vinh ph6i hop paracetamol va quinin sulfat dS di~u tri cac clnrng dun s6t..5. Nhiet dQ phong. t6n nhieu thai gian [3]. Th.. . A._ _ nehien cUu _....--.. vien Anogin quinin cua CTD.lm). 4.. . T6c dQ dong: Irnl/phut. ChAt chuan paracetamol va quinin sulfat do Vien Kiem nghiem cung cAp..!1... Acid acetic 4%.. . Djnh hrqng dang thei paracetamol (pA) va quinin sulfat (QS) trong vien bao phim Antigrip F bAng phuong phap HPLC Tren thi tnrong hien co mQt s6 che pham nhu vien AntigripF va Tiphagrip cua CTD.mrcc (1: 1) 16 mang lQC 0. nhirc dau.... -.. dau minh may.___ ...... 19. diethylamin.!c nghifm A.. ____K€t qua .. 27. Sum). Be>loc dung moi va loc mdu voi dtrong kinh Methanol loai tinh khiet s~c ky.. _.. PhU'lIng ph tip nghien c«u a.4. Thi€t - hi... natriheptansulfonat. 15.----------_.. phirong phap chuan de>moi tnrong khan.. ThS tich tiem: 20f.2.45 urn. .u h~t cac diroc dien [1.. DiJu kien - sdc kY CQt Lichrosorb RP 18 (250 x 4 mm..I. 29J co phirong phap d6i voi ch~ pham don thanh phfut. Vi v~y chung t6i ti€n hanh nghien ciru dinh tinh va dinh hrong dAng thai paracetamol va quinin sulfat trong vien nen Antigrip F bang phuong phap HPLC voi di~u kien sAc ky pha dao tao cap ion..

0 .mroc (1: 1) co n6ng d<) cua paraeetamol 30Ilg/ml va cua quinin sulfat khoang 6 ug/ml.. hoa tan trong 50 ml h6n hQ'P dung moi (ethanol .30 ug/ml y = 73. . aua Q~...u 350 300 250 200 150 100 '0 j n B .. Kit qua khao sat dp tuyin tinh Chung toi ti€n hanh khao sat de) tuyen tinh gitra n6ng d<) cac chAt cAn dinh hrong voi dien tich pic tuong irng tren cac chAt chuAn PA va QS... . ... Kit A ..45 11mtruce khi tiem sAc ky. .. Or .a._..2 ... ... ..... Chuan bi met day dung dich h6n hop chuan trong pha d<)ng co neng dQ cua PA bien thien trong khoang 6 150 ug/ml va cua QS bi~n thien trong khoang 1. IQc qua mang loc 0.... K~t qua V oi chuang trinh sAc ky nhu tren... Chudn bi dung dich Dung dich chuan: Chuan bi mot dung dich chuan cua h6n hop hai thanh phan tren trong dung moi ethanol .§ !il . tren sAc ky db thu diroc hai pic tach khoi nhau hoan toan.5 r= 0. Dung dich thir: Can 20 vien... _ .1. _ . k~t qua khao sat d<) tuyen tinh duoc trinh bay 6 bang sau: Bang 5.. SAc kY db cua dung " dich h6n .....150 ug/ml SIT 1 2 3 4 QS Dien tich pic 576.cUu .4 6 12 30 1..39 - . . -_ T b._.. .....30 2794. ..26 897.... .....90 1131.30 ug/ml. xac dinh -kh6i IUQ11gtrung binh cua vien.50 Nong dQ (ug/ml) 1.3 r= 0.4 x + 22..1.. nghien thanh b<)t min rbi tre)n d~u_ Can chinh xac mQt IUQ'Ilg bQt vien tirong irng voi khoang khoi hrong cua khoang 30 mg paracetamol..._.09 194. .. .._.2 .l..::.10 5 Khoang nong dQ tuyen tinh da khao sat Phuong trinh hoi quy H~ tirong quan so y = 92.. Pha loang 20 l§n dich IQc tren bang dung moi pha de)ng.88 458... B. hop hai thanh phan B. K~t qua khao sat de) tuyen tinh PA Nong dQ (ug/ml) 6 12 30 60 150 6 .2 2....______ 4.-..22 2214.50 5566.50 13882.. lQC.. ..9999 Dien tich pic 107.. so 0 Hinh 5.9999 . .mroc tY Ie 1:1).-_ . ...... _ . cac pic can xirng .... nehien ~__...16 x + 19...

7 99. B.36 28..43 7.38 7.2..89 152.01 29.4 99.n phap 1.10 28. c6 su nrong quan tuyen tinh gifra gia tri dien tich pic va ndng dQ (r = 0. Paracetamol 15000 10000 5000 0 Quinin sulfat 2500 2000 1500 1000 500 0 0 50 100 150 200 0 10 20 30 40 Hinh 5...2.17 28.0 98.81% co dQ l~p lai eao voi dQ lech chuan nrong d6i 1.~.88 29.52 RSD% = 1.5 1. 4. K~t qua khao sat dQ dung SIT 1 2 3 PA Luqng them V3.1.45 So li~u thong - ke X -28.81. ~ - - _ .3.5 Luong tim tM_y(mg) 1. Kit qua khao Stit dp /(ip /(li DQ l~p lai cua phuong phap diroc tien hanh tren mdu thtr la vien nen bao phim Antigrip F.~~ T.60 150.0 (mg) 7. k~t qua khao sat dQ l~p lai duoc trinh bay a bang sau: Bang 5.. B.0 98.52 % tim 1~ 98.66 S = 0.3 co de>dung cao voi kha nang tim lai cua PA la 99.6 101. Db thi bieu di~n S\l phu thuQC tuy~n tinh nbng dQ va dien tich pic nrong img ella QS xet: Cac k~t qua tren cho thdy..60 S = 1. Db thi bieu di~n su phu thUQC tuyen tinh nbng dQ va dien tich pic nrong img cua PA Nh.3 99.06 148. Nb. - + _ .5 7.0 QS Luqng vao (mg) them IB xet: Phuong ella QS Icl99.79 149. Nong dQ dung dich chuan va dung dich thu cua chung toi nk trong khoang tuyen tinh dii khao sat.3%.3. - - ~ .5 1. Kit qua khao salll(j dung Khao sat dQ dung bAng phuong phap them.12 149.48 1.10% - QS Him lugng (Il!glvien) 28.. .3.5 7.10 ...15 xet: Phuong phap So lieu thon_g_e k X = 150.5 Luong tim tMy (mg) 7.0% va . Kit aUG ::t nehien cUu O~ .n PA Ham luqng (mglvien) 153. trong khoang ndng dQ khao sat.9999). k~t qua diroc trinh bay 6 bang sau: Bang 5.66 RSD% = 1.48 % tim 1~ 99.47 1.2. .n Hlnh 5. K~t qua khao sat dQ l~p lai SIT 1 2 3 4 5 6 Nb.40 - .

ou« kien sac kf Ce)t Lichrosorb RP18 (250x4 mm. Phenobarbital trong thuoc dinh hrong d6ng thai Theophylin. dinh IUQ1lg trong m6i tnrong chuan dO. Nhir v~y muon dinh hrong cac thanh phan trong h6n hop thi phai thirc hien vi~c chiet tach plnrc tap. 10llm).41 - . tinh khi€t sAc ky. LQc qua mang IQc 0. Dasmin (Xi nghiep Diroc pham trung trong 2).base. hoa chat May sic kY long hieu nang cao MERCK-HITACHI 655A-12 voi detector UV- Vis 655A-22.45 urn. epbedrin bydroclorid -----------------. Tedralas (Labomed a Viet Nam va met s6 tai nghiem cac dang bao ch~ don thanh phdn cua cac hoat chat tren va phirong phap dinh hrong co th~ la: do m~t dQ quang.5: hoa tan 12 g NaH2P04 trong 1000 ml rnroc Natri heptansulfonat Dung dich d~m phosphat cfU.l. Binh hrQ'llg dang thot theophylin.45 urn. Thtre ngbi~m A.Phap). £)~ rat nho him cho k€t khAc phuc nhiroc di~m nay. Thiit hi.5 bang acid phosphoric. Hon nita. Trong cac Diroc li~u tham khao khac chi co chuyen luan kiem khan.g~j~r:_£~ I 4. Asmin (Xi nghiep Duoc pham trung irong 25).I. Cac chat chuan theophylin._~·__f~!_q'!_q_!. Phuong phap nghien cu-u a.2. pH 3.C chenh lech v~ hrong gitra cac thanh ph§n rat Ian trong do hrong Phenobarbital qua kho chinh xac phu thuoc nhieu vao nguoi thtrc hien. va phenobarbital trong thuAc han hQ'P tr] hen suy~n bing phuong phap HPLC Tren thi tnrong ephedrin hydroclorid. Tiphasmyl phan theophylin. A. Methanol loai dung cho HPLC. plurong phap (C6ng ty DuQ'C va v~t ill y t~ Ben Tre).acid . A. (C6ng ty DuQ'C va v~t tu y te Ti~n Giang). phtrong phap so mAu. h6n hop bang phuong phap sic ky long hieu nang cao. . chung t6i da ti€n hanh nghien ciru phuong phap Ephedrin hydroclorid. co nhi~u loai thuoc chua hen co 3 thanh phenobarbital nhir Etadasmyl. Antasma . Detector UV dij. Asmalin di~n hien co (Xi nghiep Diroc pham trung irong 5). CQt Lichrosorb RPl8 (250x4 mm. ephedrin hydrochlorid va phenobarbital do Vien Kiem nghiem cung cAp.6.t a biroc s6ng 240 nm. Sl. Be) IQc dung m6i va IQCmdu voi dirong kinh 16 rnang IQc 0. di~u chinh v~ pH 3. IOum).

HCl 7. IQc qua gidy IQc thuong.25 mg/ml d6i voi phenobarbital K~t qua khao sat S1)' nong do cac chat duoc phu thuoc tuyen tinh dien tich pic nrong irng thu duoc va trinh bay a cac bang 6.6 mg/ml. nghien min rbi trQn d~u. SAc ky db cua h6n hop 3 thanh phan (tr (theophylin) ephedrin.1. them vien. rbi IQc qua mang lee 0.2.42- va lJ cac hinh 6. tren sic ky db thu diroc cac pic tach khoi nhau hoantoan Hinh 6.6. Kit qua V 6i chuong trinh sdc ky nhu tren.mroc (70 : 30) d~ duoc dung dich h6n hop chuan co nbng dQ cua theophylin khoang 0. lAc d~u. 6.45J.0 g natri heptansulfonat d~m phosphat pH 3. T6e dQ dong 1 ml/phut.5 (38 : 62). phenobarbital ephedrin. Khao Slit tIP tuy€n tinh Chuan bi m<)t day dung dich chuan cua h6n hop 3 thanh phan tren voi nbng dQ cac chAt trong h6n hop bien thien nhtr sau: 0.05 phut) B.1 mg/ml.!m._ i·_ »« ql}_l!_ ~g_~!~l}_~0f Pha dQng: Hoa tan 1. Can chinh xac mQt hrong bQt vien nrong irng voi kh6i hrong cua khoang 80 mg theophylin.36 phut. lAc ky. va b. sAy a 50°C trong 1 gio rbi moi dem can).4 d~n 2. Dung dich chuan: Hoa tan cac chAt chuan theophylin. 15 ml mroc cAt.1.!1.4 . 6.3. - Th~ tfeh tiem 20J.2. 1 d~n 0.44 phut va cua phenobarbital 4.2 mg/ml va cua phenobarbital - cua khoang 0. B.HCI 0. trong 1 lit h6n hop cua methanol - .HCI ephedrin hydrochlorid khoang 1. 12. Dung dich thir: can 20 vien (d6i voi vien bao dirong phai rica h~t lap vo bao cua vien. them ethanol tuyet d6i d~n vira du th~ tich.5 mg/ml d6i voi ephedrin. tinh kh6i hrong trung binh cua cho van binh dinh mire 50 ml.05 d~n 0. Chudn bi cac dung dich tiem trong h6n hop dung moi ethanol .3 .6.1.0 mg/ml d6i voi theophylin 0.

Nong dQ (mg/ml) Dien tich pic 1 0.5 4 0.x aua _________ nehien cuu 0": .0 (mg/ml) Phuong trinh h&i quy : y = 2337.4 .. . D6 thi bi~u di8n su phu thuoc tuyen tinh n6ng dQ va dien tich pic cua theophylin Dien tich pic N&ng dQ (mg/ml) 1 0.25 258.5 2 105.05 ..2.3 32.5 5 Khoang nfmg dQ tuyen tinh : 0.5 H~ s6 nrong quan : r = 0..__ o .._ .54 H~ s6 tirong quan : r = 0.2 0._ . SKS : 010600 .20 208.0 4685. Ket qua khao sat dQ tuyen tinh dbi voi ephedrin STT Ephedrin. Nong dQ (mg/ml) Dien tich pic 0.8 2 1.1 3 4 1.2.2.4 42.5 5 0.3 Hinh 6.4 957. D6 thi bi~u di~n su phu thuoc tuyen tinh n6ng dQ va dien tich pic cua ephedrin r-----------.0 0.2.25(mg/ml) Phuong trinh h6i quy : y = 1030. D6 thi bi~u di8n su phu thuec tuyen tfnh n6ng dQ va dien tich pic cua phenobarbital B.9993 Bang 6.1 0.1 .HCI 60 50 40 30 20 10 L_.5 2 2.4.5 Hinh 6.0.3 2 0..2 Khoang nong dQ tuyen tinh: 0. Ket qua khao sat dQ tuyen tinh doi voi theophylin STT Theophylin 5000 4000 3000 2000 1000 o o 0._ .0 0. . SKS : 011099 Mfru 2: Vien nen Typhasmyl. Kit .1 10.9 x + 8.9998 .-- __ -- -- -- -- .2 20._~~~4 H1nh 6.1 3 4 0.0.43 H~ sA nrong quan : r = 0.15 160.2 x + 2...2 2851.5(mg/ml) Phuong trinh h6i quy : y = 111.1.- -- .4.5 1.43- . Bang 6.1 0. 0:~ ~0~2_.05 52.3 0.8 x -1.9997 Bang 6.3 Khoang nong dQ tuyen tinh: 0.3.3.5 55.lijp lai tren hai mdu vien nen va vien bao dirong: Mfru 1: Vien bao duong Etadasrnyl.2 I 1840. K€t qua khao sat dQ tuyen tinh d6i voi pheno barbital STT \ 300 Phenobarbital 250 200 150 100 50 o o 0.0 5 2..6 3736.10 3 0._. Khiio sat iI(j J(ip J{li Chung toi ti~n hanh khao sat de.

4 va 6.49 41. Ket qua khao sat dQ l~p lai tren miiu Typhasmyl STT 1 2 3 4 5 6 Ham hrong heat chat trong mQt vien (mg) Theophylin 80.04 80.50 2.83 8.10 80.46 81.90 7._~-_l_ !i!_ql}_q_!'_g_~!~f}_~0! --- ----.2 mg/ml Phenobarbital: 0.HCl 10.78 Ephedrin.HCI: 0.5. ----.47 2.48 2.02 40.88 4.90 0.85 7.31 Ephedrin.59 10.n xet: Phuong phap co dQ I~p lai t6t..6 0.1 mg/ml Kch quit khao sat dQ l~p lai duoc trinh bay (] bang 6.-----.41 41.04 0. Chuan bi cac dung dich h6n hop chuan va thir co n6ng dQtuong ung nhu sau: Theophylin: 1.90 4.79 7.4.12 1.04 1.HCI 7.32 0.95 4.12 7.53 10.91 5.18 41.00 4.51 4.02 80.6 mg/ml Ephedrin..57 2.55 2.90 Tinh thong ke X S RSD (%) 80..40 10.68 41.6 0.52 Phenobarbital 2.67 10.52 Phenobarbital 4.43 0. .47 2.5 diroi day Bang 6.91 7.20 0.72 10.51 0.82 41.81 Nh..71 10.78 81. K~t qua khao sat dQl~p lai tren mftu Etadasmyl SIT 1 2 3 4 5 6 Ham hrong hoat chat trong mot vien (mg) Theophylin 41.92 0.16 1.59 Tinh thong ke X S RSD(%) Bang 6.

0 97.6 va 6.HCl Them Tim vao thfty (mg) (mg) 2.0 98.0 98.6 tlm Ephedrin.0 Phenobarbital Them Tim vao (mg) (mg) 1.0 19.li 98.98 2.0 39.0 2.3 99.99 2.1 20.0 thay % tim l.HCI Tim Them vao thAy (mg) (mg) 5.5 20.7.0 2. K~t qua diroc trinh bay 6 bang 6.6 40.98 1.45- .85 5.0 98..0 1.0 101.0 38.5 98.99 3. ---.6 Phenobarbital Them TIm vao (mg) (mg) 0.0 4.93 % tim Il.7 dum day: Bang 6.0 0.li 99.8 Trung binh % I~ 99.__f:~!_q_1!_q_ !l_g_~j~1}_ 1 £~ . them vito miu thir mQt luong chinh xac chdt chuan bang khoang 20 .n xet: Phuong phap co dQdung cao voi ca ba thanh phan._.0 4.0 1.9 40.0 98.0 19..5 99.8 20.95 3. K~t qua khao sat dl) dung tren mlm vien bao dirong Typhasmyl Theophylin Tim Them thfty vao (mg) (rng) 39.li 102.0 99. ti~n hanh nrong nr phep thir dl) l~p lai.1 Ephedrin.5 99.99 % tim Il.0 40.0 97. K~t qua khao sat dl) dung tren miu vien bao dirong Etadasmyl Theophylin Tim Them vao thAy (mg) (m_g) 20.7 97.10 5.94 2.0 Bang 6. .3 99. B.97 1.3.0 0.0 97. Khiio sat ilP dung Khao sat dQ dung bfutg phirong phap them.5 Nh.0 1.6.0 3.1i 99.0 Trung blnh % tim ll._~.0 97.7 98.0 99.30 % hrong co trong miu thir.0 5.99 thay % tim lai 98.

. .Oml.2. Can phan tich Mettler AB 204 dQ chinh xac 0.. co th~ dinh tinh va dinh hrong nhanh 3 thanh trinh sitc ky co A. maleat bing phuong phap HPLC ----.-_ . 27. Djnh hrqng dAng thM paracetamol. c6c co mo ... d(lng C(I May sitc ky long hieu nang cao: DIONEX-Detector CQt Nuc1eosil C18 (250mm x 4mm.. Trimethylamin Acetonitril Niroc cAt. trong do vien nen Decolgen Paracetamol (PA) (PH) : maleat (CM) do cong ty United Pharma san xuat co cong thirc: 500 mg 25 mg 2 mg Phenylpropanolamin..HCL Clorpheniramin Voi nhiing hoat chAt tren..45 urn.. chuan - phenylpropanolamin hydroclorid (ham hrong chuan clorphenirarnin maleat (ham hrong 99..66%).g_~j~t}_~0! __ q'!_q_ 4. clorpheniramin . Mdu 1 co s6 kiern soat: 402221 Mau 2 co s6 kiem soat: 404971 ChAt chuan cua Vi~n Ki€m nghiem: chuan paracetamol (ham hrong 100%). Trong diroc di~n My [29] va tieu chuan co sa [4. 5J. Acid phosphoric loai dung cho HPLC. pipet thuong.!m). 6ng dong. 100. A. Thi2t hi.86%). loai tinh khiet phan tich. Th\l'c nghi~m A. UV diode array. 25...Oml. 19. co sft dung phirong phap HPLC d~ dinh hrong cac hoat chiit trong h6n hQ'Ptren.-_ hydroclorid phenylpropanolamin va Tren thi tnrong hien nay co nhieu dang thuoc co k~t hQ'P cac thanh phAn nhu tren. 99. trong cac duoc di~n thong dung hien hanh [I. lO. Dung cu thuy tinh: binh dinh mire 1000. 12]. 50._~.Oml.46- .1 mg. kY khac nhau. May do PH Meter 3305-Jenway. BQ loc dung moi va bQ IQc mau voi dirong kinh 16 mang IQc 0. .. 20._ . Nham tim met phuong phap chung. - May lAc sieu am-SONOREX. loai dung cho HPLC..Oml. . pipet chinh xac.. ~¢!_ t!....I. Hod chat. chung toi nghien ciru xay dung mQt chuang th~ phan tich d6ng thai cac hoat chat tren. 29] chu y€u chi co dang thuoc dan thanh phan. nguyen li?u Vien nen Decolgen co cong thirc nhu tren..Oml.7.. nhirng m6i chAt phan tich duoc su dung mQt chuang trinh sitc phan trong h6n hQ'P thuoc.Oml.

tnrong Dai hoc diroc Ha noi.5 025 Hinh 7. ' ~ .~ . chung toi da Iva chon ducc cac di€u kien s~e dinh hrong 3 thanh phfut PA. PH kY d~ va CM nhu sau: May sie ky long hieu nang eao DIONEX-Detector UV diode array cua bQ mon Hoa diroc._!f4!_q_l_I_q_~g~!~'Y_-:~ ! B.._~. Khao stit Iva chon ili2u kirn sdc kf Khao sat ph6 til ngoai cua cac ehftt phan tich: O. K~t qua --- ----------------------------------------------------------------------------_.•. PhA hApthu UV-VIS cua PH trong dung moi pha dQng 1.0 .c · • c 1. ~ ~ 0.2.75 1.1.2 0 200 300 Hinh 7.1. 0. 5 um).4 '" 0. PhA hApthu UV -VIS cua CM trong dung moi pha dQng Sau qua trinh thtrc nghiem.e 5 0.5 :. . Ph6 hftp thu UV-VIS cua PA trong dung moi pha dQng 2.5 0:' LD N 0 Hinh 7.3.5 2 ::. 50 . B.B '! g c . " " <3. . 0.75 0.5 5 0 1 125 . CQtNucleosil C 18 (250 mm x 4 mm.47- .0 ~ .

. Bang 7.2 ml/phut. I &3 c.. SAc ky db cua dung dich chuan PA song 244nm a buoc Dira vao cac k€t qua thu duoc. __ '__'_W_''__'I ..7 b~g acid - T6c dQ dong 1. Khtio sat 49 tuyln tfnh cua phseong phap Pha day dung dich chuan cua h6n hop ba thanh phftn co nbng dQ cua PA bien thien trong khoang 8-+80 ug/ml.79 200 34.4 Phuong trinh hoi qui: y = 0.. 10.2...16 H~ so tuong quan: r = 0.-- __ .-. Nhiet d<)phong. Cac pic da: tach kh6i nhau hoan toan...65x .-.9999 3.14 12. nehien 0' Clfu ...-. r~t I Hinh 7..~y~~-.-.48- a bang 7.-.69 7. (] 244nm d~ do PA. Tien hanh phan tich voi dieu kien sac ky nhu tren.triethylamin (968:30:2).-. Minh 7.1 5.4.-.9 19. .53 H~ so wang quan: r = 0.9999 .2 16.93 2.96 8..0.44 .. ~~e'-"""'I~.0 ID 11-e. gon.-.lg.45 4 65...-.--..72 160 27.. ta thu ducc cac stlc db nhir sau: - ~::. -- - - - - - - _.jl II ~ 1- '~!i8Il Ii II i I Ii I II ~"_'_" ~(l ! \. Kit nUG __________ :::t. sic ky d6 cua dung dich chuan PHva eM a buoc song 216nm PA.082 H~ so wang quan: r = 0.17x + 0.9991 20 40 Nong d9 (ug/ml) Dien tich pic 3.4.-....25 5 82 76. dang pic d5i xirng.4.-..56 100 17.89x + 3.(_m!) Dien tich pic 0.4 N 6f!g_ d9 (~g.24 1..(_m!) Dien tich pic 8. cua PH trong khoang 20-+200 ug/ml va cua eM trong khoang 1. dieu chinh den pH 2.09 Phuong trinh hoi qui: y = 0.6-+16 ug/ml.. - Detector UV (] 216nm d~ do PH va CM.62 N6ng d9 (f. ta thAy di€u kien s~c ky la phil hop..35 16. Th~ tich tiem mdu: 20 ul.5 g kali dihydrophosphat trong 1 lit h6n hop cua nirrrc acetonitril phosphoric.63 Phuong trinh hoi qui: y = 0.74 PH eM 8._ -op + - _ . K~t qua khao sat dQtuyen tinh gitra nbng dQva dien tich pic cac chat 3 41 40. .4.. Pha dQng: Hoa tan 2. B.5.2 10. K€t qua khao sat duoc trinh bay Hoat chat PA Dung dich 1 2 8.'"~ .6 61.

lAc d~u.49 25.89 44.62 CM 4.___.0448 Nong dQ (ug/ml)._.2657 Dien tich pic PA 44.34 RSD%"'" 0.09 2.63 4. Duoc dung dich thfr d~c.09 2. LQe qua mang Ioc 0.19 17.---_.0 ml.2632 0.2636 0.fac d~u.-.47 25.64 4._.43 S"" 2.. them mroc.023 RSD%= sA X=519.08 S = 0.!C!_ .03 522.6.7 eho thdy dQ l~eh chuan nrong d6i cua PA la 0.41 25. lAcsieu am d~ hoa tan khoang 10 phut.08 521.09 2.2636 0.5.45%... ..34 516.91 44.Lm.03 lieu th6ng ke X = 2.--_.-_.45 J.l~/!_ !!g_JJ!~..'.84 lieu themgke X =25._.62 4.-_-'.----_..54 Bang 7.70 4. ella PH lit 0.. them mroc d~n vach.2012 0. 7.2668 0._.96 Bang 7. q.----..76 44.56 44.-. Dung dich thir loang (dung d8 do PA): Hut chinh xac 1..-"_...69 44...0 ml. N6ng dQva dien tich pie cua dung dich chuin CMtchufut LUQ'Ilg can (g) PA PH eM 0.17 17.7..6..110. Bang 7.._.0 ml dung dich thtr d~c eho vao binh dinh mire 50.7.._'!_·.85 PH 17.07 2.3.. nghien thanh bQt min ._.96 Di~n tich ~e 43.. 7.13 17.57 519.41 25. them mroc d~n vach.08 2. B.22 17.24 100.-_-_.76 8. 40.:.5038 0.10mg Luong can bQt vien (g) 0.05 517.164 RSD%= 0. ella eM IA 1.0 K~t qua trinh bay 6 bang 7.50 sA Ham hrong (rng/vien) 2._._.2628 0.60 4. Can chinh xac kh6i luong bQt vien tuong irng voi kh6i hrong cua khoang 2/5 vien cho vao binh dinh mire 100.-.!_ ~0f. Dung dich thu d~c (dung d~ do PH va CM): Can 20 vien.23 17.'---._.5. K~t qua khao sat dQchinh xac diroc trinh bay 6 bang 7. Khao sat dp chinh xdc ciia phuang ph6p .64%..02 4.64% CM Ham hrong (rng/vien) 520. •:.45 25. K~t qua khao sat dQchinh xac ella phirong phap PA IT 1 2 3 4 5 6 PH sA li~u th8ng ke Ham hrong (mg/vien) 25. Luong can bQt vien va di~n tieh pie cua dung dich thir SIT 1 2 3 4 5 6 M =658.11 % .51 S = 0.__-_.40 17.45% - - - 1. xac dinh kh6i luong trung binh vien.

9..6.30 2.52 2..8: Bang 7..53 0. Kit ::l. Hinh 7.09 9.-- -.13 98.0129 0..73 100.041 0..84 10.84 0.__ _.65%. Khiio sat tIP dung ciia phuong phtip DQ dung cua phuong phap duoc xac dinh bang phirong phap them chuan.51 0.. .-- .338 101.30 2..65 23._ -- - .0131 3 0.95 99.12 9.-.50- dich mdu chuan .01 101.__ .36 99.34 9._ aua o_ CUll __ __ __._. K~t qua khao sat dQ dung Ho~t chAt STT Luong bot vien (g) Luong co san Luong trong mdu thir chudn them (mg) vito (m_£) 10. ap dung d~ dinh IUQ'l1g eho k~t qua t6t. PH va Clvl tren mdu 2 vien nen Decolgen. Cac s~c ky db thu diroc cua dung dich mdu tlnr va mdu chuan diroc trinh bay & -~~==~~--------~--------------~~ . Sdc ky db cua dung .. K~t qua khao sat dQ dung diroc trinh bay a bang 7. . .7 va 7.._ '" 4..65 99.38 99.91 2.6.0131 2 3 0.40 23.__nehien. B. Ung d(lng di dinh tinh va dinh /U'p7Igd6ng thm hnn h(YpPA.50 0... 7.34 23..61% d~n 100._. co nghia la plnrong phap co dQ dung cao..-.75 10.0137 3 Trung binh 1 0.S.0129 0.8.30 Luqng Ty l~ thu chuan tim h6i (%) th~ (m_&) 101. K~t qua dinh hrong duoc trinh bay cac hinh 7.26 2.01327 Trung binh K~t qua & bang 7.0131 2 0.8. .81 9.52 23.61 PA PH eM 1 0...8 eho thAy kha nang tim lai til 99.84 10.0137 Trung binh 1 0.040 0.4.70 2..260 98. B... a bang 7...0129 2 0.84 101.18 9.275 98.52 23. PH va vien nen Decolgen eM trong Chung toi ti~n hanh dinh tinh va dinh hrong dbng thai PA.___.043 23.-.

.-.41 (%) nhan so 103.6.04 2.-.10 509.9 cho thAy ch~ pham dem dinh hrong dat tieu chuan v~ ham IUQ11g cua PA. ..09 514.8 cho thAy gia tri thai gian hru cua cac chAt a mdu thir so voi mdu chuan la nrong duong nhau.51 - ... "WVL.:) Hinh 7. PH va CM. -- W".--.0 100.06 2.0 104. SAc kY db cua dung dich mdu thu do PH va CM (y burro s6ng 216nm I·RDeO Hinh 7.42 25.30 25.88 512...-.-.97 103.44 102.03 2.44 101.0 Tir cac hinh 7.:{ 4..-.83 518.58 102.08 2.0 103..-...-.68 101. K€t qua a bang 7.. SAc leY db cua dung dich mdu thir do PA Bang 7..09 2.__________ ::."' '·13.-..-..-..Q 11.7.. n'_o 14.68 102....-.:21t -t c .82 102.9.11 513.2 PH Ham hrong " Vat Ham hrong so vien nhan (mg/vien) 25..0 103..36 25.36 25.. K€t qua dinh hrong Ho~t chat STT a btroc song eM 244nm PA Ham hrong vien (mg/vien) 512.48 101..7 va 7.. Kit aua nehien Czlu 0'.35 Ham hrong v6i 1 2 3 4 5 6 TB (%) 102.....06 Ham hrong voi 101.. 7..5 104..20 101.06 2. ~.0 11...19 512.50 25.0 101...17 25.50 102.S.. t• ..62 102.64 (%) nhan so Ham hrong vien (mg/vien) 2.42 101. ._.

Binb hrqng dang tbOi paracetamol va ibuprofen trong vien nen bing _ phmmg phap toan pba Ngoai cac phirong phap da noi a phfm tren (phirong phap quang ph6 UV-VIS thong thuong sau khi chiet tach. Xac dinh giai song phdn tich Ghi phA h~p thu quang cua m6i dung dich thanh phfut rieng re ill 200nm d€n 300nm. paraeetamol (2) hdp thu eire dai tai 243nm va dQ hdp thu cua dung dich h6n hQ'P(3) i. tich co dQ ehinh xac 0. Ldy 10 ml dung dich pha loang bing dem pH 7 vira du 100ml. . hoa tan trong binh dinh mire bang d~m pH 7 vira dil 100ml. Xtiy dvng phuang phap a. SKS: 020601. dflng cfl - May quang phd UV-VIS Beckman DU 650i. ThVC ngbi~m A. pipet.1 eho th~y ibuprofen (1) h~p thu cue dai tai 222nm.1mg.1.can phan A. Dung dich chu§n g6e paracetamol (PG): Can chinh xac khoang 80 mg paracetamol. ibuprofen dat tieu chuan BP 1993. Cac dung cu thuy tinh chfnh xac: Binh dinh rmrc. diroc dung dich chuan g6c ibuprofen co nbng dQ 50 mcg/m!.52- . Dung dich chuan g6e ibuprofen (IG): Can chinh xac khoang 50 mg ibuprofen. Pha cdc dung dich chu8n g6c paracetamol va ibuprofen .1.2. Dung dich d~m phosphat pH 7 pha thea DDVN III. trQn d~u.2. hoa tan trong binh dinh mire bang dem pH 7 vira dli 100ml. Thiit bi. B. . B. L~y 10 ml dung dich nay pha loang bang d~m pH 7 vira dli 100ml._(_~~!_q_~q_~g_~!!_'!_t:~ 4. Hod chat.8. chung tbi da nghien ciru thanh cong phuong phap phan tich toan phd d~ dinh hrong d6ng thai paracetamol va ibuprofen. tron d~u. Mftu tlnr: Vien nen Dibulaxan.:. 1rQnd~u. phirong phap HPLC). 1rQn d~u.:. Khio sat va xiy dl}'llg phuong phap B. diroc dung dich chuan g6c paraeetamol co n6ng dQ 80 meg/ml. A. Tren hinh 8.1. nguyen vpt /i~u Chdt chuan: paracetamol.:1 biroc song diroi . ket qua ph6 ghi diroc nhu & hinh 8.

_._.L Til k~t qua khao sat m6i tirong quan gitra dQ hAp thu quang va n6ng de) cua m6i thanh phan.._ _ .._ "..... Do do chung toi chon khoang buoc song phan tich eho hai ch~t til 215nm d~n 300nm..300 ~__ .06621._.686 11. til 8 ug/ml d~n 15 ug/ml cho paraeetamol.".. sir dung d~m pH 7 lam dung mei pha loang...~__ . " " . ~__.. _ _._0._.__ . ._.52569 0..0)." +_ .. ! 0..... 215nm la luang d6i Ian (> 1._.._"'cn.1._.._. Kit ::::t nUG __________ nehien cuu 0 . ._. K~t qua duoc trinh bay (y bang 8.4. ._._._. __ Duong hoi quy D = O._._._ "~ .~_. .n.l! ____. .. .··U....37445 . . c.-l.~ . .._. chung toi chon khoang nong d~ phan tich cho paracetamol tir 8 ug/ml d~n 12 ug/ml va ibuprofen til 5 ug/ml d€n 8 ug/rnl..168 i 10.22317.__ _~_ .n ..457 . ~_~4.~-+-n_._.... ! ........_~nf.45714 i 0._.....n..._.an VavelBngtb (n.~"~ I._.." D243 i 0..53- .~.._."...336 I 12.._...29743 __ ".n. __ _~_~_.... D222 .504 __._n_n._. __ ..5066 0. "__. __ ~ __._.. None Functions._."__ ..0..._.u.g5m 7 dung dich h6n hQ'Pehufin voi cac . l.__ .._..n.7..•. Xae dinh khoang n6ng d9 co luang quan tuyen tinh VGid9 hJp thu cua m6i chdt tai cac buac song qrc dai Chung toi da pha day gbm 5 dung dich chuan co nang dQ bien thien til 5 ug/ml d€n 11 ug/ml cho ibuprofen.__ i 6. PhA UV-VIS ella ibuprofen (1) n6ng dQ 7._.) Hinh 8. .n.__ Duong hoi quy D = 0.....'._._. Trong khoang n6ng dQ d§ khao sat cho th~y co su luang quan tuyen tinh gitra n6ng dQ va d{)hAp thu quang ella m6i ch~t tai biroc song khao sat. .0186 ·_·.U.__ I __. ~._. __..n._._.".._._...._. pha mQt day.9999 1.. ._.. 5.".'.. -..u_~ __ _._._ "._.071 __ n.n. u_··.u. __ ~ __ .L r i _'_"""'_n._.._._ ".' .7._ 8._.__ .J:".. _...u._.u_.._.C . Mbi nrong quan gilra n6ng dQ va m~t dQ quang.n...15. Pha day dung dich chudn h6n h(IJJ Dimg pipet chinh xac phbi hQ'Ptil dung dich chuan g6c PO va 10.752 .....n_. ._.920 i __ ".0019 V01 r = 0.. Lmm~~--------------------~--~ SIIo:Iothin9._ ---_ _--.l __ .n. t:5' Ie phbi hQ'P gitra hai eh~t trong cong thirc ella vien nen Dibulaxan. ..1...8498 _._+I__."~ ."._.._... Ibuprofen I ~~_.·'·_~n.n.. __ . ._.. . ~.__ ._.i 0.6763 .u __J 0.._ !. __I 1._·_ .._L~_._.3348 ~_..._.".C .__ ~ __ . Bang 8. ...~.._.9994 uz/ml ._..843 .----_ -----_ ---_ --.U_L~_.._ _._.543 ug/ml va h6n hop ella cluing (3) trong d~m pH 7 b.'.._" "----!_ ._~_.. . Paracetamol uz/ml . _ -----_ -_.__~cn._..'.._.J._.576 ug/ml paraeetamol (2) n6ng dQ 10.047374.. ! 0." __ .0. Ti~n hanh do m?t dQquang cac dung dich ibuprofen tai 222nm va paracetamol tai 243 nm. i 9....n. . .00679 voi r = 0._...1.._". Sc::.. .n._._..

Nxl.......• . - -- - - - - - - - - - - - - --- - - - -- - - - - - _ .noe 0... ~. 1. -=III:tIJiu '1M! DO 6&OJ.. ~ MKiliCB'fIlN l:IIUPJlQJJIH ~JIX' DttJiftalo"I!Ilf ~AH IZrIJF!ICI'lDl 5:U. dlwJ.canQa«a.Cn U.. D.1t 1 a. K~t qua phan tich cua 7 dung dich h6n hop chuan Tren hinh 8.zg~ rn fVl (VI S_ISU>1 11. 4....cu4ead l JCG/ Dite.. Duong voi sai s6 chuan cua uoc IUQ11g SEE.r.54- ky khoang 15 .. _ .~13 li.OaJ E!td.S 9..p::melE o\. 1..81lGO It.5 ·0. __ czm . _ .. d...022 0.01411 tVI £VI Iy) o 0266 _<15 _d _d't 4> ~ ~ 'IZC DIU __ l!!o\JUIIClI.o.c=..012. K~t qua phan tich chuan nhu hinh 8..01.2040 .ut 4 0.. n6ng de) cua paracetamol thay d6i ill 8 ug/ml d~n 12 ug/ml...)OOO &.al lJaiti v.:l4!:. chusn nay dircc khang dinh chdt lUQ11gbang mQt nhom 3 h6n hop chuan cho sai s6 chuan tien hrong SEP tuong dirong Nhu v~y dirong chuan xay dung ITtren diroc danh gia la co chdt ltrong nit t6t va duoc sir dung d~ phan tich cac m~u tlnr. 4&00 8.·1I00Q IVI 8cl7of# B.~4U 8..0C'9 .0307 0... Can voi khoang 50 mg chinh xac m9t hrong dirong Paracetamol... tinh kh6i IUQ11gtrung binh vien.ND IIiCIf T~ ~OlOPt 11.'PAX ~ • O. - - - - - - --- n6ng de) cua ibuprofen thay dAi ill 5 ug/ml d~n 8 ug/ml.2.73 1.D21I .0049 M:.Z.s .._ - __ - - - - -- - - - - -- - - _ .B.. __ II._000_~ "'... ~" 7 0 4 3lJ COiiop. A.. _41 _4 ..ual 8.aUG __________ A.1 6_1140 1. _ . ~JIX.. .OOa7 -0.&'aL' r ~J4lI. I:..2 ta thAy chenh I~ch n6ng dQ cac thanh ph§n cua tAt ca cac h6n hop chuan rna may tinh tOM duoc (Calculated) so voi n6ng de) thuc (Actual) la rAt nho. O~ 02 _h:>d iItoan<ing _... Phdn tich chudn Dung d~m pH 7 lam m~u trang.034 0.. 4 ~ __4 l 0. l§n luot dira cac dung dich chuan theo thir ttr vao phan tich.r 01:~.6700 0........0 .OOSG nnJ~ ~DIJJiIIICII'1II 7.. cho vao binh dinh rmrc IOOmI... khong phai loai bo dung dich chuan nao.iUKle.. . them 75ml d~m pH 7 lic .1ng ~ .0234 0_0040 'l'.Q30 0034 O.) ua . Chudn bi mdu thit Can 20 vien. "1Ib. ~ 0_018 O. Or .6t'#S 8. 'dill Wi! '>'Sa ~ ..d o:. nghien bi}t vien da: nghien min tuong ky thanh bQt min.~~=..0_ 300 . 0. \ PAlttlR1 1IrIIS1:19 S8Ipl~ ul.o.~ ot e•..201..CIt.au . lolL 211>. Kit nehien . e...82!>'& 6 1324 10.0w.2"000 CXH:BJIIPItI\oUON Cal.0200 7. IUIIM liII:lIH:tiIx nat."00 6_6434 1I. 0144 -O.7 Hinh 8.4816 6 U75 10_ 6749 6.1eg2 0.1"4 9.OlS ."l:.0. a..2.0011 0_0(»1 -0_0044 -000&6 0.

_ _ _.2.1046 0. __ . Dung dich thit duoc chuAn bi nhu muc tren vii. Ham hrong ibuprofen {[It] c.1313 = 2.69 mg S (ug/ml ) 9.94 329.1179 0.6907 gam) voi 9 phep thir. Cac ket qua duoc trinh bay trong bang 8.38 330.37 207.32 209.2.54 207.1147 0. VT Iii. Ket qua khao sat dQ l~p lai cua ParacetamoI BQt vi en IT 1 2 3 4 5 6 7 8 9 (g) va Ibuprofen.6947 11._.3472 10.. LAy chinh xac 2ml djch IQc pha loang bang d~m pH 7 vira du 100ml. S6 li~u thong ke Paracetamol £)0 Ibuprofen £)0 duoc Hv hnmg (mg/vien) 329.2142 6.9063 9.055 RSD% = 0.1113 0.24 328. tron d~u. n6ng dQ cua paracetamol M m = [Pt]x M xVT m doc duoc tren may (mg/ml). .55- .1112 0.62% Ibuprofen Xtb = 208.9619 6.59 211.03 diroc H.08 207. 1. the tich pha loang cua dung dich thir (VT =100xIO0/2 = 5000 ml). B6 khoang 30ml dich 19C dAu.8929 0.60 Paracetamol Xtb == 329.7072 12. IQc.nAng dQ cua ibuprofen doc duoc tren may (mg/ml)}. phut.lugng (mg/vien) 209._ _ -. _ _ __ >- __ •••• _.1027 0.2927 6.~0!._~·. la kh6i IUQTlgtrung binh vien (gam).1731 7. Kit qui thl}'C nghi~m Cl.9604 10.q_~8. tien hanh phan tich theo phtrong phap dd xay dung. dtroc dung dich thir..3768 6.\ kh6i hrong bot vien da din d~ dinh hrong (gam)._. duoc tinh bang each thay [Pt] bang [It].~j~f}.01 332.98 205.5 mg S = 1.62 207.91% Ket qua tren cho thdy phirong phap co dQ l~p lai cao d6i voi ca hai thanh phAn.899 RSD%=0._.4714 (ug/ml ) 6.6795 6.0825 6.~4!_ql!.6091 7. Xdc iljnh ilP /9P /{li cua phuung phdp SKS: Tien hanh thir dQ l~p lai cua phirong phap tren mdu vien nen Dibulaxan 020601 (Mtbv = 0.6429 10. them d~m pH 7 den vach.01 328.0234 9.25 330. tri)n d~u. Ham lUQT1g trong mot vien: Xtrng/vien) Trong do: [Pt] Iii.1010 0._ .59 326.1038 0.73 332.45 210. Iii.5693 10. Bang 8.

33 - --_ ...066 a Kean: ~ ~ O.--.-. .076 0.012 0._- Xtb = 330.20 --_. C2.3374 6.013 0-018 l25Ol«1OPIIN 0.0011 10.c:II'fAaI %BOJIR:)PIIN »MCIl'I'NC muJlJIOPDf ~ca'rIIX :tJIUPR:)1'IIN PADCII'f'AIC DlJDR)1IJDI 9..---- 3 4 r--c-----~ _.016 0.- 331.75 6.c!u.01'6 0.0177 6 _ --.3768 ------ 10.A~ o.967' 0..:2:142 10.SlQJ4 10. Paracetamol n 1 f)QC deoc Ibuprofen rng/vien Tinh thong ke DQc dugc (~_gIml ) mg/vien 210.24 209.073 '.2023 11o.. . dQ l~eh chuan nrong d6i ella phep thir la kha nh6.--E$nw. ._291C 9.910) t.3609 --6.0234 .15" 0. 0.acaWoX ~ 4 4 1 2 Hun: DOPICPJIM PuP.3.3."'.3402 Tren cung mQt duong chuan.~1P 10. - 10.- _ . ----.385 RSD% =0.6Sl08 10.01'6 0.. c:~ ~4!_ _' .al : -.8a: 7. Xdc d.-_ -~---_. .CB'fAH DtlPR:)1IlDf PAJaCB7AH PAMCIlftK UUlIC>PDf ~'!NI DQllJIDPJDf ~'IAX 2: KMn-_ 3 3 1 2: )Cun: w. K~t qua khao sat dQ 3n dinh cua dung dich."-._- 10._ .V. .2361 11.014 0..9~0 6.065 2: 2: 1 Ht. ---.B._.·····_·' __ L· ___ 330.0009 _'. -.2940 ---_.2P38 9.w. UUlIJIIIOIIBN '. q_l_I_q. Ti~n hanh phan tich mAu tren duong chuan da xay dung trong vong 60 phut.0268 --- _ ..54 --- Tinh thong ke _{J.---.OGS 0.562 S S 1 2: )C_.". Hlnh 8.- Xtb == 209..-.02:3 A.5"1'00 '._-- . c:cacc~uon 9_~33 6.082 0... 330.3473 - -- --._~ ____ . .20 330.02 207.94 --..076 0.nh 4p In dinh cua dung dich Chuan bi mQt miu thu nhu tren.!l_g_~j~f} . Ket qua phan tich ciia 5 phep thir.:.CP48 1 1 1 PAMCIS'lNf 0. 6. -..- 10.12% . Cll' 10 phut doc miu 1 IAn trong cung di~u kien. - ._.078 100..lon ~ %3tJJI1OI'IIN PAaCZ-.56 ~ ..G4? . _ .44% -- --- 330.9063 '. phan tieh trong cung di~u kien ella cung mQt miu K~t qua a bang 3 cho thay dung dich co dQ dn dinh cao.II . . .II S... __ .013 0. K~t qua duoc ghi a bang 8....0042 5 --_ ---_--10.SQJ3 '. 029 14 IQI' ~bm 1t0lp • DUur.-.-------- 330.. PAaCIIBK DUJiROnN PADCIl'INII IJlUPlIIDPIIN PAMca". -.f ._..1'731 11. - 6.B CO!IIpCInIl: p.3C.57 209. ."2 7.. 2 -- -~--'.2927 9."83 6.3472 1.G" 6.1862 9.~----. Bang 8.924 RSOOIo == 0.05 _ _-- ---..SI~8 10.- 210.sa6 6.81 -209.1g(!lll) ..3.n t .3.42 S == 0._ 6..- .58 S = 0.01'1 0..31 _.IIft.CIS'MK .- 'lI::Ital S. . $TANDARDDItOZ OF : : '-" .

1% d~n 101.3.4% PARACET AMOL 5.047 100.-.-..-....._~._ -----_ 4..8 '-~-~"~5Jj'O~·--~·' ----·--iO~096T--~--· ·---···5j94--~ ···-· ...0.----.----.--..-._---- 1 ._--_..-f ···-······· ·--·...575 9.1045 2 0. mQt hrong xac dinh ch~t chuan Ibuprofen....-..-. ·················----100. 5.8% Nlnr vay... K~t qua dugc trinh bay trong bang 8..040 .·····. Xae t1.2% d~n 99. th~y cua Ibuprofen bi~n thien til 97.-.-..1 -._Fl!_9..-T6T. Paracetamol bing 90%.~--.2%.---.-.... K~t qua khao sat dQdung ciia plnrong phap TT BQt vien (g) Chuan them vao (ug/ml ) Tong do diroc (ug/ml ) Luong tim thay (ug/ml ) Ty l~ tim thdy % . ...-..--.623 ··················--5-:45-6"·············------T6"~4·37-8-----·-······-···-·-·-····--·-··s.3.4."5()"f··-···-·········-····· 101._.4.-.1052 .··· ··················· .h ro ham hrong. dQ dung cua phuong phap ch~p nh~n diroc d6i vci ca 2 ch~t..--~ -_ _.2% va 100.57- ... TB: 100..-------. Ty 1~tim Paracetamol bi~n thien tir ...-....g_~j~1J_~ ~ C. Them vao hrong bQt vien da bi...._.-----~.6440 4...!q_!l. 100%. --····-o~i6·i4---··· -·-·~r~···· """"'0}027--' TB: 98.··-····· .-.."3 ..-.nh ------------------------------------------------ella phulYng phap dp dung Khao sat dQ dung bang each them chuan.._ 10.-.2.-.---.. .0346 . _. Bang 8.-~~-~...---._.5 sao cho nbng dQ cua m6i hoat ch~t mung (eng khong nim ngoai khoang nang dQ trong day dung dich chuan va ti~n hanh phan tich bang plnrong phap da chon..-. 110% rbi tien hanh nhu muc 2.-.-. 0..

can phan tich. phuong phap quang ph6 thong thirong [3] va s~c ky long hieu nang cao (HPLC) da: diroc sir dung. HITACHI 3210 (Nhat Ban). Bb sung HCI O. .IN. binh dinh mire cac loai: 50ml. dyng cy Nguyen v~t lieu: "Thu6c thir"). bo 20mi dung dich dfiu. ChAt dbi chien hoa hoc: Quinin Sulfat va Paracetamol chuan (do Vien kiem nghiem . phai sir dung nhieu dung moi hfru co dQc hai (cloroform). mircopipet: 10m!. them 70mI HCI O.58- . l~c ky khoang 15 phut. Vi v~y chung toi da: nghien ciru xay dung mQt qui trinh dinh hrong dAng thai paracetamol va quinin sulfat trong vien nen Antigrip F bfuIg phuong phap phan tich da cAu tir (MCA) tren may quang phb thong thueng. . Binb hrQ11gdAng tbOi Paracetamol va Quinin sulfat trong vien nen Antigrip F bAng phuong phap phan ticb t1a cAu tir (MCA) Vien nen Antigrip F cua Tiphaco san xuAt duoc sir dung lam thu6c ha s6t co chua 2 thanh phdn voi cong thirc nhu sau: Paracetamol Quinin sulfat 150mg. Phuong phap HPLC cho k~t qua nhanh va kha chinh xac song thi~t bi chua th~t phb bien 6 tAt ca cac co sa ki~m nghiem trong rnroc va chi phi cung kha tfm kern._'.!_·__4. hoa chit. TbuAc thir.IN vira dil t6i vach.I. . . 500ml.t phan tich da ciu tir (MCA) B. 30mg.p). l~c deu. 2mI. D~ dinh hrong hai thanh phan hoat chAt tren.!_!l. lOmI.9. hut chinh xac lOmI dich Icc ti~p theo cho vao binh dinh . Dinh hrong bang quang phb uv-VIS thong thuong cAn thiet phai chiet tach rbi do rieng tirng chAt tai cac cue dai hAp thu d~c tnmg. dung dich Hel O. B.BQ Y t~ cung d.. . so sanh k~t qua thu duoc voi phuong phap do quang phb thong thirong (bang chi~t tach) thea tieu chuan co sa. Phuong phap nay tAn nhieu thai gian va cong sire. . Sml.. Thiet bi: May quang ph6 ttr ngoai kha kien GBC Cintra 40 (Australia). xir Iy k~t qua bAng phftn mem tv xay dung.IN (theo tieu chuan DDVN III - ky thu. IOOmI.!I_q_!!g_~j!_.!_£0!. . 4. A. Khao sat pha hlip thy UV va llfa chon cdc btrue song phlin ttch can chinh xac khoang 75mg Paracetamol cho vao binh dinh mire lOOmI. Dung cu: pipet ImI. Xay dl}'ng phirong phap t1inb hrqng dAng thOi Paracetamol trong h6n hQ'p bAng va Quinin sulfat vien nen Antigrip F (Tipharco) Thuoc tlnr: ethanol tuyet dAi. LQc. .

_!_·__If4!_q_'!_4_!'..g_~!!_l}_E.0!

.

---.

mire 100ml rAi bd sung dung dich He] 0, IN vira du, litc deu. LAy chfnh xac Sml dung dich vira pha cho vao binh dinh mire 50ml, them dung dich H'Cl 0, IN cho toi vach, litc deu, diroc dung dich Paraeetamol 7,5f-Jglmltrong moi trutmg HCI 0,IN Can chinh xac khoang 40mg Quinin sulfat cho vao binh dinh mire 100ml, them 70ml dung dich ethanol 96%, litc ky khoang 15 phut, Bd sung ethanol vira du toi vach, litc d€u. LQc, bo 20ml dich IQc dau, hut chinh xac 20ml dich IQc ti~p theo cho vao binh dinh mire 100ml rAi bd sung dung dich Hel O,IN vira du, lAc deu. Ldy chinh xac Sml dung dich vira pha cho vao binh dinh mire 50ml, them dung dich Hel O,IN cho toi

vach, litc d€u, duoc dung dich Quinin sulfat 8 f-Jglmltrong moi truong HCI 0,IN.
Ti~n hanh ghi phd hAp thu UV rieng biet cua m6i dung dich tren trong khoang biroc song nr 200nm toi 400nm voi miu trang la dung dich HCI O,IN. K~t hop ca hai phd ghi diroc tren cimg mQt dA thi ta thu dtroc k~t qua nhu 6 hinh 9.1 .

\:/j;

. -1\~~1.~..--.-..",
A/
22~O

--......
3392 ,

_J

Hinh 9.1. Phd hdp thu quang cua Pracetamol (1), Quinin sulfat (2)
trong moi tnrong Hel O,IN.

200 0

'
2~OO ZlS.O 300.0

. .c ... '--sas.o
3500 :l"1S.o

~oo.o
"'"

J

.r

Nh{in xet: Trong moi tnrong Hel O,IN, Quinin sulfat co btroc song 208nm, 250nm, 314nm, 341nm con Paracetamol
bmrc song nh6 han 215nm Paracetamol buoc song

C1,lC

dai hAp thu tai 4

co met eire dai hAp thu tai

buoc song 241nm. Noi chung, hai thanh phan co su phan bi~t nrong d6i

ve phd,

a

a vung

co de>hAp thu quang Ian nen ta khong chon

nay. Dua tren du li~u ph6, chung toi chon 6 btroc song phan tich

cho hai chAt la: 215nm, 231nm, 241nm, 250nm, 314nm va 340nm.

B.2. Xac tlinh khoiing nang
va S dung dich Quinin hydrochloric bay trong bang 9.1.

tip phOn tfeh
(khoang nAng de>5-25 ug/ml) trong dung dich acid nAng de> 1-10 ug/ml)

Do dQ hdp thu quang cua 6 dung dich Paracetamol sulfat (khoang

,

0,1 N

a ca 6 buoc

song dd chon, k~t qua khao sat dQ tuyen tinh diroc trinh

- 59-

_____•____

4. Kit qua nehien elm _.... O~_.

....

....

......

..

......

.......

-

- - - - -- -

... ... _. _-

Bang 9.1. Tfmg hQ'P k~t qua khao sat m6i wang quan gitra dQ http thu quang va nfmg dQ cua Paracetamol Paracetamol va Quinin sulfat tai 6 biroc s6ng da chon,

Bmrc
song
_frun)

H~

tuong

so

quan (r)
0,99940 0,99990 0,99997 0,99997

215 231 241 250 314 340

Phuong trinh h6i qui y=ax+b _y == 0,036x + 0,037 y = O,066x + 0,032 y = 0,082x + 0,030 y = 0,075x + 0,027 Khong hAp thu

Quinin sulfat Btroc H~
song
(run)

so

tirong

_guan(l"}
0,99997 0,99997 0,99997 0,99999 0,99982 0,99955

215 231 241 250 314 340

Phuong trinh h6i qui _y=ax+b y = 0,080x + 0,002 y = 0,039x + 0,001 _y = 0,064x + 0,003 Y = 0,099x + 0,001 _)'_ 0,015x - 0,001 = Y = 0,018x + 0,001

Nh(in xit: nhin bang ta thAy c6
s6ng k~ tren (h~ s6 nrong Paracetamol quan r

S1,l'

tuong quan tuyen tinh rAt ra rang gitra d<}hAp va Quinin sulfat tai 6 biroc Tai hai biroc song 314nm va 340nm

thu quang va khoang nAng de>khao sat cua Paracetamol

=

0,9999).

hAu nhir khong hAp thu (hinh 1), tuy nhien tren thuc t~ dieu nay khong (5-25 ug/ml) va Quinin sulfat (1-10 ug/ml).

anh huang toi phirong phap phan ttch, do do chung toi chon khoang nAng de>phan tich cho Paracetamol

B.3. Chuan hi day dung dich chulin hOn hpp a. Dung dich chudn g6c Paracetamol
Can chinh xac khoang 25mg ParacetamoI them 35ml HCI O,IN, lAc kg khoang chuan cho van binh dinh mire SOml, 15 phut, Them dung dich HCI O,IN vira du toi

vach, lAc deu. LQc, bo 15ml dich loc dAu, hut chinh xac Sml dich IQc ti€p theo cho vao binh dinh rmrc 50ml khac, them dung dich HCI O,IN cho tci vach, lAc deu, duoc dung dich chuan g6c Paracetamol (PG 50 ug/ml).

h. Dung dich chudn g&c Quinin sulfat
Can chinh xac khoang 2Smg Quinin sulfat cho vao binh dinh rmrc 50ml, them 35ml ethanol 96%, lAc kY khoang 15 phut, Them ethanol vira toi vach, lAc d€u. LQc, bo 15ml dich JQc dfiu, hut chinh xac 5ml dich loc ti€p thea cho vao mot binh dinh rmrc SOml, them dung dich Hel O,IN cho toi vach, l~c dSu. Lai lAy chinh xac lOml dung dich nay cho vao binh dinh mire SOml khac, them dung dich HCl O,IN vira du, lAc deu,

ducc dung djch chuan g3c Quinin sulfat (QG 10 ug/ml).
c. Pha day dung dich chudn h6n h(/JJ D~ tang d<}chinh xac cua chuan, loai tnr sai s6 mac phai khi do ta se ap dung thuat binh phuong t6i thieu bing each sir dung sf> hrong dung dich chuan him hop nhieu han s6 cAu tir, Boi v~y chung Wi da pha m<}t day gAm 5 dung dich chuan h6n hQ'Pdung cho phan tich chuAn.

- 60-

_~.__44!_9.'!_q_~g~!~1}_ £~

-

---- --------------------------_.

Dung pipet chinh xac phoi hop til hai dung dich chuan g3c (] tren trong binh dinh rmrc 50m] va sir dung dung dich HC] O,IN da pha loang ta thu duoc me}t day dung dich chuan h6n hop theo bang sau:

Hang 9.2. Pha day dung dich h6n hop chuan.
Dung dich chuan h6n hop s6 ml dung dich chudn g6c cdn Paracetamol (PG 50 ug/ml ) Quinin sulfat (QG 10 ug/ml )

idy

Cl C2 C3 vao binh dinh mtrc 50ml 6 10 7 9 8 8

C4 9 7

C5 10 6 10 1,2

N6ng tJ(J cua m6i thanb' phdn trong dung chudn h6n h(1JJ tuong tsng ( pg/ml ) Paracetamol 6 7 8 9 1,4 Quinin sulfat 2 1,8 1,6 B.4. /)0 d{j hlip th(l quang cua cae dung dich chufIn han hpp

Ti~n hanh do d{>hdp thu quang cua 5 dung dich chuan h6n hop vira pha tai 6 biroc song da chon. Sir dung mfru trfutg la dung dich HC] 0, IN ta thu diroc cac gia tri de}hdp thu quang nhir 6 bang 9.3.

Hang 9.3. Gia tri de>hAp thu quang do diroc cua cac dung dich chuan.
Buoc song (nm) / d2 chuan Cl C2 C3 C4 C5 215 0,2896 0.3098 0,3299 0,3390 0,3491 231 0,3219 0,3676 0,3987 0,4196 0,4522 241 0,4308 0,4841 0,5120 0,5318 0,5732 250 0,4641 0,5085 0,5281 0,5400 0,5753 314 0.0224 0,0206 0.0190 0,0169 0,0154 340 0,0251 0,0234 0,0216 0,0185 0,0165

Nh(in xet: nhin vao hang de}hAp thu quang ta thfty

a cac

biroc song tir 215 - 250 (n6ng d{>ph3i hop tang
-

nm thi de>hAp thu quang cua cac dung dich chuan til C] - Cs tang ddn, di~u chirng to tai

cac btroc song nay thanh phdn hdp thu chinh la Paracetamol
vay ta thdy tai hai buoc song nay Paracetamol

dAn). Con tai biroc song 314 va 340 nm de>hAp thu quang til C1 Quinin sulfat hdp thu la chu y~u (n6ng de>ph3i hop giarn ddn). B.S. Xay drplg duO'ng chufin bdng phan m2m tTen may tinh

C, lai giam ddn, nhu

hAu nhu khong hdp thu

rna

chi co

a. Thiit ltjp cac thong s6 phon tich
DAu tien ta vao chuang trinh bang each nhay kep bieu nrong cua chuang trinh tren man hinh desktop, sau do ta chon

rna ij.p

tin maio Cira s6 chuang

trinh nhir (] hinh

9.2, chon "Dfmg y" da

rna t~p tin maio

Ta nhap cac thong s6 dil' li~u chinh nhu sau:
- 61 -

ta hru lai bang each nhAn nut "Nhdn" hoac "D6ng l~p bang each chon "Thay y".. N~u cAn ta e6 the sira d6i cac dlr lieu da thi~t oJt' hoac "X6a". ... mo tao (hinh 9. _ __ _ __ _ 4. Hinh 9.. Cira s6 chuang trinh phan tich da Hinh 9. ten miiu.4. (hinh 9.5) d6 chuyen sang nhap buoc song moi. sau m3i IAn nhap chon "Them" chon "D6ng - s" de hoan thanh cira s6 nhap. eu6i cling N6ng de>cua cac dung dich chuan h6n hop: lam nrong W nhu phan nh~p bmrc s6ng. S8 li~u v~ cac buoc song pharr tich. Hinh 9. __ .62- .3) Ten cua m3i chAtthanh phan: Para + Quini ._ -- . __ . Kit __ __ __ .aua nghien Clfu __________ ::t. . __ ..5. Hlnh 9.. Nh~p s8 li~u v~ cac chdt thrum phk. Thi6t l~pcac thong s6 chung.3. (hinh 9.. c~u tir MCA. __ . (hinh 9. (hinh 9. __ __ __ __ .4) Cac btroc song dung trong phan tieh: nh~p IAn hrot theo thir t\1" 6 biroc song.7) Khi da nh?tP xong cac du li~u cAn thiet eho qua trinh phan tich.6) De>hAp thu quang cua dung dich chuan va dung dich tlnr.2. Cac thong s6 chung: nguoi thuc hien.

. phan tich xuAt hien nhir dn thiet. Hinh 9.':.~_~~~:L: ~' ._1. Phdn tieh chudn Sau khi dA nh~p du dfl li~u phan tich ctra sf. ~ . rbi lAy gia tri trung binh ella cac n6ng de) tinh toan duoc. . #w·i. •• ~~~·'::.~~~.._c:~ ---------------------------------_. • - _ .. Dtr li~u n6ng dQ m6i thanh ph§n trong dung dich chuan h6n hop.6... .. K~t qua phan tich eho 5 dung dich chuan h6n hQ'P tai sau biroc song dA chon diroc tinh toan va t6ng hQ'P trong bang 9.__ :. Nong de) thuc Cr cQt ben trai va nbng de) tinh to an dircc nam ngay (] cQt ben canh._:. .' . "'~'. Phsn mem chi cho phep phan tich n6ng de) ella tAt ca cac dung dich chuan tai hai biroc song cung luc..••• < ••••• .:~:_:. do do tfch ci de do diroc tai 6 biroc song ta eftn phai phan = 15 lfin.. a hinh 9.63- . .·_. Hinh 9. •• . .. ••••• ~. . b. ta bitt dftu ti~n hanh phan tich chuan bang each nhAp vao nut "Phdn tieh" tren thanh menu hoac tren thanh cong cu.' __I!:4!_ 9. Nhap s6li~u v~ dQ hftp thu quang do duoc tai cac buoc song.S. tl6 ella dung K~t qua cua m6i lfin phan tich duoc bieu di€n trong khung "Nfmg phai dich chudn".l!t!_ t!g~j!''!..----------------------------_.'-': - '.4.--------_. ella sa phan tich dung dich chuan va tlnr.~.. .7.8. Hlnh 9..~.

K~t qua phan tich 5 dung djch chuan.010 -0.614 8. Loai bo mQt dung dich chuAn. Tinh toan lai dtrong chu~n.000 7.1g/mlJ -0. .020 1.019 0.4.800 8. cit 5 dung dich chuan d~u co the dung cho phan tich MeA.390 9.024 -0. Thimh phdn Para Quini Para Quini Para _Quini Para Quini Para Quini Nongdo th\l'~ml}_ 6.014 -0. N~u dirong chuan chua thirc t6t thi ta co the t6i dung dich chuan.64- Hinh 9.9 ta chon dung dich chuan 5 sau do nhap vito nut "«".9.000 1.022 0.012 -0.600 9.020 0. ------__.' _ .400 10.200 Nong dO tfnh duqc~ml) 5.785 8.000 2.981 1.10.000 1.976 1.986 1._ .000 1. Nlnr 0 hinh 9. S\l sai khac gitra hai gia tri n6ng dQ thuc va nAng dQtinh toan diroc th1JCt~ co the chAp nhan. _._ :t_-__ 44!_ 9_l_I_Cf_ !l_g_~!~'!_!:~ Dung dich chuan heln hop Cl C2 . c.012 6. Vi du: ta Uti hoa dira tren S\l thay d6i s6 co the bo b61 rnQt each ngdu nhien mot hoac hai dung dich chuan nao do. N~u dirong chuan da co chat Iirong. no se bi loai bo khoi cQt "Dung dich chudn chon".978 2.015 0.209 SI! sai khac(J.014 -0. . Bang 9. thi khong cdn phai thay d6i lai. Hinh 9. T6i uu hoa duong chulm Ta co the kiem tra va t6i Uti hoa dirong chuan bing each co the thay d6i d€ sai s6 gitra n6ng de>th1JCva nbng dQ tinh toan diroc cang nho thi dirong chuan se cang chat hrong.009 C3 C4 C5 NhQn xet: Dua vito bang ta thay su chenh l~ch nong d9 cac thanh phan cua tat ca cac h6n hop chuan rna ph:1n mem tinh toan diroc so vai nbng de>thuc Iii khong dang k~ nen ta khong phai loai bo dung dich chuan nao.000 1.

65- . LAy chinh xac mot hrong bQt vien da: nghien min luang irng voi khoang 7.010 1.5. d~ sieu am 10 phut.019 -0.6. nehien cuu 0 ----------------_ _ .l sai khac. ta se do d<)h§. IN vira du.IN vira du. Chudn hi mJu thit Cao bo lap vo boc duong ben ngoai.IN lam dung moi pha loang.y str sai khac h§. dung duong chuan da xay dung d~ tinh toan k~t qua . NongdQ thlJc()J. them HCI O.000 1. pha 3 dung dich h6n hop kiem tra co n6ng d<)cac thanh phan gdn gi6ng cac dung dich chuan C2. lAcd6u. sir dung dung dich HCI O.409 SlJ sai khactug/ml) -0. £)0 il9 hdp thu quang ella mdu thit Dem dung dich thir nay di do d<)h§. cu6i cung dem so sanh chung voi gia tri nAng dQthuc.pthu quang tai sau buoc song da chon.600 9. them 70ml dung dich Hel O.:.p thu quang cua chung.790 8.010 0. e3.000 1. can 20 vien. ducc dung dich tlnr .bo 20ml dich IQc d§. d.u.unhu la r§. B.p vao nut "Phdn tich". Ket qua kiem tra.lAy chinh xac IOml dich IQcti~p then cho van binh dinh mire 100ml. Dua vao su thay d6i ta se phat hien ra dung dich chuan gay ra sai s6 va loai b6 no. cac gia tri v~ nAng d<)se diroc tinh toan lai nlur 0 hinh 9.400 Nong dQ tinh dUQ'c(~g/ml) 6.glml) 7.. sau do sir dung dirong chuan vira xay dung dS tim lai cac gia tri v€ nAng dQ. Kidm tra. ghi lai cac gia tri dQ hAp thu quang d€ chuan bi nhap van phan mem. •:._ -------------_. nhir v~y duong chucin da xay dung diroc daub gia 1(\co chAt hrong t6t.000 1. K~t qua duoc cho boi bang 9. them Hel 0. e4• Coi day la cac dung dich thir.009 Thanh ph&n Para Quini Para Quini Para Quini Bang 9. Nhpn xet: K~t qua cho th§.4. nghien ky thanh bQt min trong c6i sir. lAc ky.983 1.010 0. Cdch tinh kit qua Ham hrong cua Paraeetamol va Quinin sulfat trong mQt vien duoc tinh then c6ng thirc sau: .5. •:. Kit aua __________ ::t. danh gia chat hrong dtrong chuan.tnho.022 -0. Dem IQC. --- Sau do ta nh§. danh gia dua tren Dung dich han hop kiem tra KTI KT2 KT3 S1.800 8.IN. tinh kh6i hrong trung binh vien.10.619 8. lAcdeu. Phan t{ch mbu thir Antigrip F . ddnh gia chdt luang dutmg chudn Dung pipet chinh xac d~ ph6i hop ill hai dung dich chuan g6c PG va QG.5mg Paracetamol cho vao binh dinh rmrc 100mI.017 0.978 1.

•:. hoat chelt trong mqt vien.11. hoac Quinin sulfat doc duoc tren may (ug/rnl). (*) = m m : la luong bqt vien da: can trong dinh hrong (gam) . Kit quiz phdn tich tren mdu Antigrip F Sau khi phan tich tren may tinh ta se thu diroc gia tri v~ n6ng de) m6i thanh phan trong dung dich thir (ug/ml). (cell). M C x 10 x - ._j_.66- ke tren Excel. Tinh toan thong ke cac k€t qua thu diroc co the th1JC hien nhanh chong bing each sir dung cac ham thong Sir dung cong thirc (*) a phfut tren de tim ra ham hrong ke (statistical) Trong co s~n trong phfrn mem Microsoft h9P thoai "Insert Function" Excel. Xu ly thong . Vao phdn mem nay bing each chon bieu nrong cua no tren desktop. (hinh 9. chon Insert\Function. Hinh 9.__l!/!_ q~4_~g_~!~'!_ ~ ~ HL (mg/vien) Trang do: C 10 M : hi n6ng dQ cua Paracetamol : la h~ s6 pha loang.11) MQt s6 ham thong dung: Gia tri trung binh DQ I~ch chuan Phuong sai So sanh hai phirong sai So sanh hai gia tri trung binh ham Average ham Stdev ham Var ham Ftest ham Ttest chon mQt 0 belt ky chon "Statistical". : Ia kh6i hrong trung binh cua mQt vien (gam). .

34 30.51mg voi rmrc tin c~y 95%.53 29. Ham hrong cua Paracetamol trong vien la 147. .67- .60:t 1. .n xet: K~t qua cho thAy de) l~p lai vci cit hai thanh ph§n la nrong d6i t6t. NhQ.69 28.51mg_ Dc) l~ch chuan Sai so chuan Sai so nrong doi Khoang tin c~y n=6'p=095-1'J .mg_ hoat chat fronK m(>tvien (m_g)_ Quinin sulfat Paracetamol 29._~·__Jf4!_q1!_4_!!g_~!!_'!_!:~ Bang 9.20 1.r 1 2 3 4 5 6 Tinh thong Ire Gia tri trung binh X Ham /llt. Con dQ dung duoc xac dinh thong qua kha nang thu h6i cua k~t qua phan tich khi dung phuong phap them chuan.13 147.49 0. Nhu v~y phuong phap phan tich MeA co th~ su dung d~ phan tich mdu Antigrip F.70 147.69 148.71 29. gian da:dtroc danh gin va chap nhan.70% d6i voi Paracetamol va 1. D~ danh gia phuong phap MeA. K8t . D{>chinh xac thirong dtroc xac dinh thong qua d{>l~p lai cua phirong phap (each thong thirong nhAt la xac dinh d{>lech chuan nrong d6i cua k~t qua phan tich RSD .68 ± 0.68 0.60 ± 1. tIP chinh xdc elia phuang pluip B. Ti~n hanh so sanh d9 chinh xac va dQ dung cua hai plnrong phap thong qua test F (so sanh hai phuong sai) va test T (so sanh hai gi:i tri trung binh).03mg con Quinin sulfat la 29. tren mdu Antigrip F.98 0.theo cac duoc di~n hoac sai s6 nrong d6i).71% d6i voi Quinin sulfat. _ qua dinh hrong S6 thutt.03mg a 29. Chung ta cling co th~ danh gia mQt phirong phap phan tich (Phuong phap A) b~ng each so sanh k~t qua phan tich voi met phirong phap phan tfch khac (duoc tien hanh cung phong thi nghiem va cung khoang tho.10 146.93 148. SKS: 050801. phirong phap B).:.6. ciing nhir cac ch~ pham chua hai thanh phfm nay co tY l~ gdn giong nhir tren.85 146.7.43 147. =257 ..60 0.90 147.51 30. trong thuc nghiem nay chung toi dtl chon plnrong phap do quang ph6 ill ngoai dinh hrong rieng hai thanh phdn Paracetamol va Quinin sulfat lam plurong phap so sanh. Nguyen tdc M{>tphuong phap phan tich thirong diroc danh gia bang each khao sat d{>dung (accuracy) va dQ chinh xac (precison).68 :to. .40 0.41 29. sai s6 tuong d6i my thee tirng tnrong hQ'Pla 0. Bdnh gid dp dung.

65 28.46 148.77 29.05 FTN 0.67 6 1._~ .__ .95..5.S. _ _..05 Quinin sulfat (mg/vien) 28.__.18 MCA(A) 29. Kit _:t _ _. .95). Ket qua khao sat dQ l~p lai cua 6 miu thir theo phuong phap B.05...38 ITN= = 5.5) Quinin sulfat UV (B_) 29.95. Phuong y nghia thong ke 6 mire a phap x n S2 Paracetamol UV(B) 149.S.9..84 149..:. So sanh dQdung.7.03 % Bang 9.9).05 (Bang 9. Bang 9.23 2.10=2.05.49 ITN = 1.--- -- -- -- -- -_. Ket qua khao sat dQdung theo phtrong phap B. __.68 6 0. cac tac gia da: khao sat dQ dung va dQ chinh xac. .__ __..35 MCA(A) 147.05 Test F SI..96 1'(0. tu« hanh Hai thanh phan Paracetamol va Quinin sulfat da: ducc cac tac gia dinh hrong bang phirong phap tach rieng hai thanh phfut sau do do quang ph6 nr ngoai.23 6 0..60 6 0.93 29. __ cuu aua nghien __ __.98 148..1O = Test t Nhfjnxit: 1.06 151.71 < 1.-.5) = = 1.32 28..2 FTN =0..24 5.7 va S...79 29.79 150. de>chinh xac cua hai phuong phap.4 _.94 < to. Paracetamol (n = 5) Quinin sulfat (n = 5) 99. y nghia So sanh 2 gia tri trung binh (test T) cho thdy k€t qua dinh hrong gitra hai phuong phap khac nhau khong co y nghia thong ke d6i voi cit hai thanh phftn Paracetamol va Quinin sulfat (P=O.23 - So sanh hai phuong sai bfing test F cho thdy chung khac nhau khong co thong ke (P=O. Ket qua phan tich dircc trinh bay trong bang 9. Bang 9. Nhir vfty de>dung va dQ ehinh xac cua phuong phap MCA khong khac so voi phtrong phap do quang ph& hap thu tir ngoai dinh hrong rieng tirng thanh phdn.00 % 99.33 < 1'(0.89 Ket qua so sanh gitra phuong phap MCA va phuong phap quang ph6 thong thuong (da diroc danh gia) cho thdy su khac nhau khong co = 0.95). . STT 1 2 3 4 5 6 Paracetamol (mg/vien) 149.17<10.5.68- .

..Djnb hrqng .20~g/ml). I~c d~u dircc dung dich co nong oQ khoang 20J. Khiio sat phD hap thfl UV va i1!'achpn cdc bUtTe song phlin tich Cit PA va ME d~u co kha nang hAp thu quang trong moi tnrong kiem va moi tnrong acid! ethanol. .. Them dung dich d~m phosphat 5.1. MOi trutmg d?m phosphat 5.. d~m phosphat 5. dung dich NaOH O. Thi~t bi: can phan tich METTLER AB 204. Hic sieu am d~n tan hoan toano B6 sung ethanol 96° vira dti den vach. may quang ph6 Hitachi U-321 0 (Nhat Ban). 4.52%). ME chuan (ham hrong: 99._ 4. Kit__qua nehien_ cUu ___. Xay dung phuong phap djnh hrQ'DgdAng thiri PA va ME bing phuong phap quang pb6 MCA B. dung C\l Vien bao phim Pamesic cua Tiphaco sf>10 san xuat: 02 02 03 Cong thirc: Paracetamol Acid Mefenamic Ta diroc 500mg 250mg vira du vien Thu6c thir: ethanol 96°. " _.. Them 120ml ethanol 96°. Thu&c thif._ -.._ . mircopipet: 10ml.__ -- _ - -_ . Dung pipet hut chinh xac 5ml dung dich vita pha cho vao binh dinh rmrc 50ml. may thu dQhoa tan PHARMA TETS PT III. gifty IQc. ph~u.8 (theo tieu chuan DDVN III . Hic d~u duqc dung dich P' 0 c6 n6ng d<) khoang 200jJg/mI. •:. 5ml.69 - . ChAt df>i chieu hoa hC)C:PA chulm (ham hrong: 99. Do do chung toi khao sat dQ hAp thu cua dung dich PA va ME trong moi tnrong d~m phosphat 5.IN. dAng tbiri Paracetamol 1 va acid Mefenamic trong vien nen Pamesic bing do quang pho MCA Ngoai phirong phap HPLC da trinh bay i:J tren. hoa chit. c6c co mo."Thubc thir"). may l~c sieu am BRANSON 5210.IN .8 - Dung dich PA: Can khoang 40mg PA cho vao binh djnh mire 200mI.. - Dung cu: pipet lmI.. lOml.68% do Vien Ki~m nghiem .BQ Y t~ cung cap). trong d~ tai nay chung toi gioi thieu mQt k€t qua nghien ciru trng dung plnrong phap MCA diroc sir dung tren phfm mem sAn c6 cua may quang ph6 GBC Cintra 40 d~ dinh luong d6ng thai paracetamol va acid mefenamic trong san pham thuoc Pamesic. Cac ta diroc cua vien (Tiphaco cung cAp). 21.8 va mei tnrong NaOl-l O. 50ml.8 vira du. binh non. B. A.. may quang ph6 ill ngoai kha kien GBC Cintra 40 (Australia). 100ml. binh dinh mire cac loai: 20ml._ " " _ __ __ _ __ __ .__ O~__ .1g1ml(n6ng dO thuc h123. 2ml..10.

84). Them dung dich dem phosphat 5.2.~. l~c sieu fun d~n tan hoan toano .~". l~c deu duoc dung dich co n6ng dQ khoang Sug/ml (nong de>thuc la 8. Phi>cua PA (23.. l~c deu duoc dung dich M'J' Dung micro pipet hut chinh xac 4ml dung dich vira pha cho vao binh dinh mire 50mI.1.. l~c deu duoc dung dich co n6ng de>khoang l Oug/ml (nong de>thirc la 9.18Jlg/ml)..1 8Jlglml) trong moi truong NaOH O.. Them 120ml dung dich ethanol 96°.Dung pipet hut chinh xac Sml dung dich vira pha cho vao binh dinh rmrc SOmI. Dung micro pipet hut chinh xac 4ml dung dich vira pha cho vao binh dinh rmrc 50mI. Phi>cua PA (l5. PA ME ~~..Lglml).. l~c deu diroc dung dich P'l co n6ng dQ khoang 200J.IN.lN vira du d~n vach. Hic deu dtroc dung dich M' 0 co n6ng de> khoang 100J. ~ .lN vira dii.Lglml.~J"""...~ . l~c sieu am d~n tan hoan toano B6 sung dung dich NaOH O.65J. MOi trutmg NaOH O. l~c deu dUQ'cdung dich co n6ng de>khoang 16J. l~c sieu fun d~n tan hoan toano B6 sung dung dich NaOH O.IN .1 va 10.8 (8. B6 sung dung dich ethanol 96° vira du d€n vach.. •:.IN vira du d~n vach. Them 120ml dung dich NaOH O...~ :- Hinh 10.. Quet ph6 cac dung dich tren (] buoc song til 220nm d~n 400nm va chong ph6 cua hai ph6 P A va ME 6 cung moi tnrong ta duoc cac ph6 db nhir hinh 10. Them dung dich NaOH O.. ( Dung dich ME: Can khoang 20mg ME cho vito binh djnh mire 200mI.lg/ml) va ME (9.8 vira du.Lglml nong dQtlnrc lit 15.IN vira dii. Them 120ml dung dich NaOH O.IN. moi wang d~m phosphat 5. ~ .Lg/ml).. Them dung dich NaOH O.2.:z- . ~ •• ~".Lg/ml.84J._(!f4!_q_l}_4_1}_g_~!~1J_ 5:~ Dung dich ME: Can khoang 20mg ME cho vao binh dinh mire 200mI.lN Dung dich PA: Can khoang 40mg PA cho vao binh dinh mire 200mI.20 ug/ml) va ME Hinh 10.70 - .65~glml) .

999998 Phuong trinh h6i qui y=ax+h y = 0.23 714.999999 285 .0346x . cac dung dich chuan ME lei Mj. voi cac dung dich chuan PA la Ph P2.. K€t qua khao sat khoang tuyen tinh PA Biroc song (nm) 257 H~ so nrong quan (r) 0.1269Abs (All 334.8 PA c6 dinh pic ME 246. ---. B.43 360._f_.0060 y = 0.IN. K€t qua thu diroc a bang 10.lN PA c6 dinh pic ME a 257. Pha day dung dich chuan va dung dich chuan h6n hQ'P Dung dich chuan I PI I P2 I P3 I M1 1M2 1M3 HI1 So ml can lay vito binh dinh mire 50mI -I P'l(ml) 5 12 15 I1 l l M'l(ml) 5 12 15 II I I I Them dung dich NaOH O. a -_.__ ~!_ ~g_~!~'!. M2.IN se thao tac pha ch€ don gian hem so voi dung dung dich d~m phosphat.1682 0.8 279.-----_._.0.8 0.999996 0..---------_..0366x .4 220. . Khiio sat khoiing tuyJn tinh va tinh chAt cpng phJ cua PA va ME Pha day dung dich chuan va dung dich chufut h6n hQ'Ptheo bang 10.52 134.---------------------- Trong moi trutmg ilcrn phosphat 5. M3 va cac dung dich chuan h6n hQ'Plei HI h H22. Bang 10.3 Abs) 205. 4 ql!.H33 Bang 10.0004 .3407 Nhin xet: .2. Til ph6 d6 ta chon dai song phan tich til 220nm d~n 300nm.0213x .6 416.5713Abs (AI 1= 677.IN vita du den vach H22 2 2 H33 I I Do de> hAp thu quang cua cac dung dich thu diroc (] 2 biroc song lei 257nm.Dc) hAp thu quang cua dung dich (] moi tnrong base t6t hon moi tnrong acid duoc chirng minh ca trong ly thuyet va thuc nghiem.5 285.-------__.2.1 0.8nm voi dQhAp thu la 1.1.0715x + 0.0006 Bu6c song (nm) 257 H~ so 285 0. chon moi tnrong thuc nghiem lei dung dich NaOHO.2986 0. Vi v~y.0008 y = 0. Mat khac khi tien hanh voi dung moi la NaOH O. __.2.71 - nrong quan (r) 0.Inm voi dQhApthu la 1. .999985 ME Phuong trinh h6i qui y=ax+h y = 0...5 - Trong moi truang NaOH O. P3.3 Abs) 353.q_ _c::~ - .2953 = 309.. 285nm.0.1..3479 1.0.

..1461 0..21 DQ hap thu h6nhqp PA.0725 TongdQ Mp thu PA+ME 1.. Xay dtplg phuang phap i/inh 1U'(TIIg dang Ihm PA va ME b&ng plucang phap MeA tren may quang phd GBC Cintra 40 a. Uie d~u dc§ntan het........IN vira du....2767 0..__________ 4.....423 0. c Trong dung dich h6n hop PA va acid ME dQhdp thu quang co tinh eQng tinh. B.__ . Kc§tqua khao sat tinh chAt cQng phd BUGe Nong dl) (ug/ml) PA-ME 20 . Dung micopipet ph6i hop 2 dung dich Pl1 va MI J vao binh dinh mire 50ml. Chudn bi mdu ... Diiy dung dich h6n hap chudn Can 50mg PA ehuin vao binh dinh mire 50ml (ky hieu la PI)' Can 25mg ME chuan vao binh dinh mire 50ml (ky hieu la MJ)' Them khoang 30ml dung dich NaOH O.IN vao hai binh dinh rmrc tren dc§nvach..2117 0...331 1._. Ldy chinh xac 5ml Ldy chinh xac Sml (y (y binh PI vao binh dinh mire 50mI. ..9999) gitra n6ng dQ va dQ hAp thu cua PA va ME trong khoang nbng dQ khao sat.. bd sung dung dich NaOH O. Them dung dich NaOH O..03 100.....l Oug/ml.__ ..-.647 0.98% RSD=O..94 100..05% 0=3 XTB= 100.lPA 1.665 0. __ -.. . I~e d~u diroc cac dung dich luang (rug la Pll va Mll.07% RSD = 0.88 100. l~e d~u tao hai dung dich luang dirong la PI va MI.05 99..3..20Ilg/ml va cua ME Ia 2 . . __ .wml) p 11(pIg/ml) 8 10 12 14 16 Mll(!Jig/mI) 8 7 6 5 4 ...057 0.ME 1..422 0...0415 0...058 0.. .1379 De>hap thu ME 0..10 8-4 4-2 20 -10 8-4 4-2 song (nm) 257 De>hap thl..02 99.332 1._-_ - Bang 10.28 Thdng ke XTB = 99....211 HH xl00 T 100... Vi v~y chon nong dQ dinh IUQ'I1gua PA la 4 .-.648 0.285% 0=3 285 Nh{in xet: Kc§tqua cho thAy co Sl1 nrong quan tuyen tinh rAt chat che (r = 0..6922 0. sir dung dung dich NaOH 0.3. binh MI vao binh dinh mire 50mI...0845 0. Pha day dung dich chuan d€ xay dung dirong chuan Dung dich hon hop chuan C2 C3 C4 Cs So ml dung dich chuan goe can lay vao blnh dinh mire 50ml Pl1(ml) 4 5 6 7 8 Mll(ml) 7 8 6 4 5 Nong dQ cua mlii thrum phdn trong_ dun_gdieh chuan han h<JP nrong imgf.:.666 0...IN vao m6i binh. Kit qua nehien cuu _ 0':" . .2894 0. ...4._.3652 0..4355 0.1 N d€ pha loang thu diroc day dung dich nhir sau: Bang 10.5818 0.72 - CI .

!!! 1 .them NaOH O.:. Ldp phuong phdp phdn tich tren may B~t may Quang phA.:. L~y chinh xac l ml dung dich thir 2 nay cho vao binh dinh rmrc SOmI. be. tren man hinh hien thi cira sA chuang trinh nhir hinh 10. lAc d~u duoc dung dich thir 2. •:. Trong muc "General": + S6lAn I~p lai (Number of repeats): + sa IAndo lai mdu chuan (Number 1 of standard replicates): 1 ug/rnl 1 + S61An do lai mdu tlur (Number of sample replicates): + Don vi nong dQ (Concentration units): .IN vira du._~. Cira sA "Application Control" . Hlnh 10. nhay dup vito bieu tuong chuong trinh do Quang cua may Quang ph6 GBC Cintra 40 tren desktop cua may tinh di~u khien .IN vita du. Dung dich kiim tra -. . L~y chinh xac lOml dich IQcvito blnh dinh mire lOOml. trong 6 "Description" cua cira s6 nhap ten phirong phap phan tich mdu. chon irng dung Multicomponent..73 - .IN.. Dung dich thir Cao lap phim boc ngoai cua vien. din 10 vien. xac dinh kh6i hrong vien trung binh. Nghien ky thanh bQt min trong cBi sir.3. I~c sieu am 10 phut.IN vita d1. Hic d~u dem loc. them dung dich NaOH O. Thi~t l~p cac thong s6 cho phirong phap trong muc "setup" -<} Method .ld~n vach diroc dung dich thir. 20ml dich loc dAu.__!:~!_ql}_<!_ !:!g_~j!_'!_ _c_. L~y chinh xac mQt hrong bQl vien tirong trng voi mot vien chua khoang 500mg PA va 250mg ME cho vao binh dinh mire lOamI. them dung dich NaOH O.:.-__.._ Dung dich kiem tra I(ky hieu lit KTI): 7ml dung dich Pl1 + 6ml dung dich Ml1 Dung dich kiem tra I(ky hieu lit KT2): 6ml dung dich Pl1 + 7ml dung dich Ml1 . Vito Menu APplication. them khoang 70ml dung dich NaOH O. b.3.

. . Trong muc "Algorithm": -¢- Chon "K matrix" Instrument . . Dtt li~u nao la chuan thi tich dftu (X) vao c<)ttrong muc "Std" cua cira s6.74 - .6._·__If~!_ q1!. DAi song (Scan range): chon ph6 til 220 d€n 300nm. . Nhftp nut "Sample" tren khung "Setup".._ f. V~ tfic quet (Scan speed): lOOO... Cua s6 "Sample Setup" ... kiim tra chdt luang duong chudn.Onmlphut.. . _. -. Hlnh 10. Hop thoai "Method Setup" Hinh 10. Hlnh 10. £~ _._.. Cua s6 "Instrument" c.:. .5.4. ...q_ ~g_~!~~. do mdu thit . Phuong phap do (Operation Mode): chon quet ph6 (Wavelength scan) . Nhap cac dir lieu v~ ten cac chuan. Ki€u do quang (photometrict Mode): chon m~t d<} quang (Absorbance) . Trong muc "Component": Nh~p ten cac thanh phfut tham gia phan tich: PAvAME. ... Lap duong chudn tren may. mdu cAn do va nbng dQ thuc cua chuan..

•:.:. £)0 dung djch KTI va KT2 d~ kiem tra chdt hrong duong chuan cua may da xay dung bfutg each cho mdu vao thi~t bi quang hoc rbi nhap vao nut "OK" trong hop thoai nlnr hinh 10. £)0 m§.3.S.6 va bang 10.7_ Cho chuan tlnr 1 cAn do vao thiet bi quang hoc r6i chon "OK" tren ht)p thoai nay.9.5. may 10. Hinh 10. cho dung dich mdu tlnr vao thi~t hi quang hoc r6i nhdp nut "OK" trong h<)p thoai nhir hinh 10. HQP thoai xac nh~n nh~p m~u kiem tra Hinh 10.8. sa hinh 10.75 - . Cach tinh kSt qua: Ham hrong cua PA ME trong vien tinh theo cong thtrc: Mg/vien Trang do: C 5000 : m He s6 pha loang m N6ng de>cua PA hoac ME dtrec doc tren may Kh6i hrong b<)t vien dff diroc can =C * 5000 * M TB MTB: Kh6i hrong trung binh mt)t vien .7 .3 man hlnh se xudt hien hQP thoai nhir hinh 10.7. •:.4. Nhay num "Run" tren cira ----------------- .10 va dUQCxu Iy se thong bao k~t qua phan tich nhu hinh a bang 10.9. Hop thoai xac nh~ nhap chuan . Hinh 10._1_·_!f4!_q'!_q_!'_g_~!?_1}__C:~ •:.u thir. Hop thoai xac nhan nhap mau thu Sau khi do xong cac dung dich. Sau m6i IAn do xong mt)t chuan lai c6 mot h<)p thoai tuong tir va l~p lai qua trinh nhu chuan thu 1 d6i voi cac chuan thu 2.

24 14. Vi v~y dirong chuan dugc danh gia lit kha t6t va dang tin cay.a!II.aeJ~ Olea ..T (ug/ml) 12.19 6.. khong dang k~.~-: 1~17 14'B 1 1 Ml K1IfIIm 1 ! S&td!tdl: 111> U4 susn 4: 1117 7.llT4 ~ UT5 Iua 1139 11.b!r o!iiaIml~ U!le~ Dim reriOal: Ntab!!fd aepJt npliCiIei: Slimlifa C~batU N....76 - . K€t qua kiem tra drum gia chdt Iuong dirong chuan Dm.&iIl !Qs..k<t_Mk Nalw d t.20 7.49% 0.~M! .28 14.__ 4.23 6.5.lO:B lOS5 U.n xit: K€t qua cho thdy s\!' sai khac gitra nbng dO thuc va nang dQ do dtroc rdt nho.28 416 5':» S..__ Q __ __ StiG~ _ __.23 Sai sA cua phirong phap 0.!:m 11141:24 }419 6.24 N6ng de>do diroc . III U1 N:l_ 6: 1Cl'1 NJ.l~ Rl.ev-.10.41 ~_13:T~ S11 5..13 i!'9 ill ill i96 N:J ~: Tl 1137 l'\b.. .__.d: 31it~'dh: 6.afa4 5.kd!: N..42':0.Tlff*100% ME PA ME Nh.14 7.1~ lJ..__ __ __ __ . N.D (ug/ml) 12..N'«~ N..55% 0. __ __ Or __ __ .aIIpnU: NIIu· d.71 dQC Hinh 10. K€t qua tren may GBC Cintra 40 Bang 10..tg djch kiem tra KTI KT2 TP PA N 6ng de>thuc .__ .16% ID . 1()Q') tIIl. 100_ ~ ~~ B9IIlr. "'wleiJIi : DiCO ..28% 0.JlOIIMIi: ~_t -~~ SIlIIiIn!I: SIl!ltatd 1: . Kit qua nzhien cuu ...nmew: p l.__..

B.62 5.39 11.98 98. Xir 19 nhu do mau Pha chinh xac mot dung dich h6n hop thir nrong irng voi 12(Jlg/ml) PA nhu muc phan tich mftu Pamesic.35 98.74 5.89 5.17 12. Xtic dinh dp dung clia phuang ph tIp Ti~n hanh: .S.0762 0.7.p l{li clia phuang ph tIp Ti~n hanh pha va phan tieh 6 mdu thu.39 12.0311 1.80 Nh.09 12.6.38 12.96 5. .PA (12.1 102.:.55 494.78 101.1288 1.6 ta thfty ham IUQ1lgcua PA va ME trong vien mau Pamesic hoan toan dat chi tieu chftt hrong (PA til 98.81 5.62Jlg/ml).26 12.n xet: K~t qua khao sat dt) dung cua plnrong phap eho thfty phirong phap cho k~t qua dt) lap lai kha t6t voi cit hai thanh phdn PA va ME.05 Gin tri tnmg binh DQ l~ch chudn Sai s6 chuan Khoang tin c~y Sai s6 tuong d6i N6ngdQ Xu ly thong ke do dtroc (ug/ml) 5.4.!_~~ Bang 10.27 0.23 2 3 4 5 6 Til bang 10.7.78 d~n 102. II 5. XtIc dinh tIP lq. Dung dung dich da dem xac dinh dt) l~p lai lam dung dich thu (T 1) co n6ng de> ehinh xac 13.77 - .88 11.73 5. Dt) l~p lai cua phtrong phap PA STT 1 2 3 4 5 6 N6ngdQ do diroc (ug/ml) 12. ME (5. B.75 244.45 492.3947 0.85 DQ I~ch chuan Sai s5 chuan Khoang tin c~y Sai s6 tirong d6i 0._ (Fl!_ q_7!_q_~g_~!~.51 98.35 Xu ME ly th5ng ke 12.78 5.9%. ME til 97.72 .90 98.9853 0.0320 0.30 514.05 253.55 12.41 PA 493.95 245.91 ME 102.3%).88 247.70 497.98 d~n 102.82 101.9876 % dat diroc (%) PA 11.37 10.71 Gin tri tnmg binh 5.74 5.1227 0.55 ME 255.8935 1.0501 0. SIT 1 mCan (g) 0.93 248. K~t qua phan tich mau Pamesic Nang dQ do diroc (ug/ml) Him hrong tinh diroc (ug/ml) ME 5.54 99.0120 1.5 99. Pamesie ta co k~t qua 6 bang 10.16 11. Bang 10.30 97.9798 0.90 505.26Jlg/ml).82 5.71 PA 98.

59 Gia tri trung binh ME 99.9609 2.61 99. ta thu duoc k~t qua Te2 TC3 .------.IN.02 ME 3.1288 0.07 4. •:.87%.5148 0.2972 0. df>ivoi ME la 100.-----.65 99. .78 - .53 5.8.9597 2.2150 0.-----_. TC3_ --- ------__---. Hoa tan va them vao vira du d~n vach bfutg NaOH O. Hic deu diroc dung dich chuan C co PA (300 ug/ml). TC3_ Bern do va xu Iy tren a bang 10.87 15. Til dung dich Tl hut chinh xac 50mI cho vito 3 binh dinh mire 100mI dtroc ky Can chinh xac 30 mg PA va 15 mg ME vao binh dinh mire 100mI.33 4.8.05 100. •:.2094 Xu 1j thong ke DQ l~ch chuan Sai s6 chudn Khoang tin c~y Sai s6 tuang d6i Nh{in xet: K€t qua khao sat dQ dung cua phuong phap cho thAy phuong phap co dQ dung cao.25 0.43 100.11 4. ty l~ thu hdi df>ivoi PA la 99._f~:4!_9.67 1.40 9.53 6. ME (150 ug/ml) .06 6.83 3.IN vira du cac binh TCI.87 ME 100. Bang 10.06 9.03 3.:.2230 0. TC2. Them NaOH O.01 1.19 7._i.54 99.1!/!_ !!g_~!~'!_~z!!!_ hieu lit TC 1.25%.67 100. Them Iml dung dich chuan C vao binh TC 1 2 3 dirong chuan vira tao. DQ dung cua phirong phap Nong de) do dircc Mdu do TC1 TC2 TC3 (Ilg!_ml) PA Nong de) them vito _(a) (Il_gt'ml) PA Nang de) thu hoi (b) (ug/ml) PA Ty l~ thu hoi a/b*100% PA ME 9.04 3. TC2.34 12.

. 10Jlffi). lOJlm).· :5. chi cAn lua chon diroc dung moi hoa tan va pha loang thanh cac dung dich thir (hoac dung dich chuan). ?l!<J!!..c!!!.mroc .TC. dtroc sir dung rAtrQng rai trong phan tich va kiem nghiem diroc pham. Th~ tich tiem 20Jll..acid phosphoric 0.16 - 99. Vi v~y chung toi thuong chon Cl. Dinh tinh va dinh hrong d6ng thai paracetamol (PA) va ibuprofen (IBu) chung toi chon diroc di€u kien sAc kY sau: CQt Lichrosorb RP 18 (2~Ox4 mm. Detector UV d~t a buoc song 279 nm. . = Phirong phap da duoc daub gia la co dQ chinh xac cao (sai s6 nrong d6i % 0. Pha dong: Acetonitril .'!. Da s6 cac chAt phan tich (cac thuoc) da khao sat la nhtrng chAt co tinh phan (la cac muoi cua base htru chirong trinh sllc khao sat. T6c de) dong 1 ml/phut..1 % (60: 40).1. Tinh thich hop cua h~ thong dat yeu cdu.2 bang acid phosphoric. kY long pha dao voi he dung moi phan C(J CQt RPI8 la loai cQt thong dung trong cac s6' kiem nghiem da diroc sir dung d~ phan tich cac duoc pham Qua nghien ciru. dQ dung t6t (zy 1~thu h6i 98.1.51-1..16%).. va co th~ ap dung rQng rai cho cac trung tam kiem nghiem thuoc. Phuong phap sic ky long hifu nang cao (HPLC) Day la mQt phirong phap phan tich hien dai. Uu di~m chung cua phirong phap HPLC Ia co su 6n dinh va co de>chon lee cao. Phuong phap da duoc irng dung lam tieu chufut cho vien nen bao phim Pamesic. Phuong phap dinh hrong d6ng thoi paracetamol va acid mefenamic da duoc xay dung voi cac di€u kien sau: CQt Lichrosorb RP 18 (250x4 mm. nhfrng noi da duqc trang bi may sllc ky long hieu nang cao.TC hoac chdt co tinh acid). ti~n hanh nhanh chong va co th~ ap dung d~ dinh tinh va dinh hrong cac hoat chdt trong h6n hop rna khong ccln phai chiet tach rieng biet. 5. Detector UV d(lt 6' biroc song 224 nm.tetrahydrofuran (3 : 8 :9) di~u chinh d8n pH 2. . T6c dQ dong 1 ml/phut.79 - .g __ __. .. C:!T!:~. 5._. .. Tinh tuyen tinh d&direc khao sat trong mQt khoang luang d6i rQng. BANLU!N CHUNG 5... khao sat bang tlnrc nghiem.-.2.. C(J Cl. - -.. chung toi d& xay dung duoc chuong trinh phan tich bang HPLC cho cac h6n hop nhir sau: 5.. .42).. .. Viec chuan bi mftu tlur cilng don gian.1.1. /J. Pha dQng: Acetonitril.

Han hop paracetamol (PA) va cafein (CA).lg natriheptansulfonat 4%-diethylamin ti I~ (650: 350: 1). _ .... Tuy dien tich pic cua cac hoat chdt thu ducc co dQ chenh I~ch I6n do ham hrong cac hoat chAt co tY I~ khac nhau va co dQ hdp thu tu ngoai khac nhau. 10J. cua quinin sulfat la 1.07 %).9999 voi met khoang khao sat kha rong cho phep ap dung voi nhieu ch€ pham nrong tu co tY I~ cac thanh ph§n khac nhau.--.. -. dieu kien sAc ky da ducc khao sat bao g6m: CQt Lichrosorb RP18 (250x4 mm. phfuI tram tim lai cua PA va CA tren hai m§. Sum). cac pic c6 dQ phan giai ro rang..._ .lm)..0% den 99.80 - . -_ -_ -.-.4.4%). .98.5.mroc (35: 65).. T6c dQ dong: lrnl/phut.. - Th~ tich tiern 20J.1.9 den 99.... Ti~n iru hanh so sanh ket qua voi phirong phap chiet tach (tieu chuan co sa) ta thAy phuong phap da sir dung d~t dQ chinh xac nrong dirong. Pha dQng: 1. Phuong phap c6 th~ ap dung d~ dinh hrong dbng thai PA va CA trong thuoc c6 chua hai thanh phan tren... = Da khao sat tinh tuyen tinh trong khoang n6ng dQ phan tich (r lai t6t (sai 0.-~---.-- ludn chung -.9999).0. Phuong phap xu Iy m§. Th~ tich tiem: 20111. Th~ tich tiem 20111.. vay phirong phap c6 dQ dung t6t. DQ l{lp lai voi sai s6 nrong d6i cua paracetamol la 1. Detector UV: 235nm. phan tach t6t cac chdt trong h6n hop.88% va dQ dung tir 99.ll.3%.. dQ dung cao (ty l~ thu h6i 98% ...81).-_ -_ -_ -_ . Pha dQng: Dung dich acid phosphoric 0.--_ . Nhimg cac pic each xa nhau chirng to khong co str anh huang Ifillnhau khi dinh hrong.1.-._ -_ -_ .5 %.. dQ l~p 5& tuong d6i 1.75% trong han hop dung moi methanol.. Detector UV d~t 6 buoc s6ng 273 nm.54 den 1. H~ s6 nrong quan tuyen tinh r=0. co nhieu che pham Alaxan hru hanh tren thi tnrong.__ . 5. 5. -Elm . trongl lit h6n hop methanol-acid acetic Tren sAc ky db. T6c dQ dong 1 ml/phut.03 . Nhiet dQphong. d€ thuc hien trong thai gian ngan..16%. di~m han va co th~ Slr dung cho cac cong thirc thu6c khac c6 thanh phfuI nrong nr. Phan tich dbng thai paracetamol (PA) va quinine sulfat voi dieu kien sAc kY la: CQt Lichrosorb RP 18 (250 x 4 mm. - -_ --_ -_ -_ --. Va irng dung d~ phan tich K~t qua khao sat danh gia cho thdy phirong phap co dQ l~p lai t6t (sai s6 urong d6i til 0.3..u dan gian.u til 98.

Detector IN d~t 6 biroc song 240 nm. hydroc1orid.1. Sai s6 nrong d6i cua PA la 0. . phenylpropanolamin hydroc1orid (PH) va clorphenylamin maleat (CM). sir dung chuang trinh sau: May sAc ley long hieu nang cao DIONEX-Detector IN diode array. Pha dQng: Hoa tan 2. Phuong phap dinh co dQ l~p lai cao.67%. T6c dt} dong 1 ml/phut. . 5.61% d~n 100. Vi v~y phirong phap nay co th€ irng dung thay cho phuong phap cua tieu chuan co s6. SKS : 010600.0 g natri heptansulfonat trong l Iit han hop cua methanol .r 244nm dS do PA.triethylamin (968 :30 :2). Pha dt}ng: Hoa tan 1. i.6. 10J. SKS : 011099 va vien Typhasmyl. Tuy nhien trong thirc t~. theophyllin va _ phenobarbital chung toi dung chuang trinh sAc ley nhu sau: Da:ti~n hanh khao sat tinh tuyen tinh.5 (38: 62). H6n hop 3 thanh ph~n gdm co paracetamol (PA). di~u chinh d~n pH 2.65%). phenylpropanolamin hydroc1orid va clorpheniramin maleat trong vien nen.19%.81 - . T6c dQ dong 1. Da: img dung phan tich co k~t qua tren hai miu vien nen va vien bao duong la vien Etadasmyl.. cua CM la 1.7 bfuIg acid phosphoric.~!!_q_~!:'.1}g f Phuong phap nay co thS dung d€ dinh tinh va dinh luong cac thanh phan trong h6n hop thay cho phirong phap chiet tach trong tieu chuan co-se._~·__J_q!!_?lf-. CQt Nuc1eosil C 18 (250 mm x 4 mm. 5 urn). 5.5_ Han hop thuoc co 3 thanh phful ephedrine Ct}t Lichrosorb RP 18 (250x4 mm.-Ull). dQ l~p lai. dQ dung.5 g kali dihydrophosphat trong 1 lit h6n hop cua mroc acetonitril . Co thS dung chuang trinh nay de dinh tinh va dinh hrong d6ng thai paracetamol.dem phosphat pH 3.4 7%. tiem: 20 I-ll.1. Th€ tich tiem 20l-l1. Kha nang tim lai duoc kha t6t (dao dQng til 99. do ham paracetamol la qua cao so voi hai chdt con lai nen phai do rieng chdt nay voi dung dich tlnr da: dircc pha loang 50 lfut. cua PH lit 0.2 ml/phut. Detector UV d~t a biroc song 216nm dS do PH va CM.Th€ tich - Nhiet dQphong.

- _ ... - - - - - - - -- - _";. _.- - - -- - - - - -- -

5. es« ludn chung

-- ......

-,._

- - - -- - - -- --- - -- -- - - -- -- - - - -- - -- - -- - - - -_ .... --_ .... - - - - - - _ ....

-- -- -

... .. - - -- - - -

-- - - - - - - -- -- -- -- - - -- --_ .. -- _. la: paracetamol,

5.1.7. Dinh hrong h6n hop 5 thanh ph§n trong nang thuoc colussin cafein. Dieu kien siic ky: May sAc leY long hieu nang cao HP 1100 - Hewlett Packard. CQt Lichrosorb Si 60 ( 250 x 4mm; 5 urn ). Detector UV - VIS: 257 nm do PE; CM va PA. 298 nm do CA va BH.

bromhexin hydroc1orid, pseudoephedrin hydroclorid, clorpheniramin maleat va

Pha dQng: Methanol- dung dich d~m amoninitrat pH 9,5 (45: 6). T6c d{>dong: 1,5 ml/phut do PE va CM. 1,0 ml/phut do CA va BH. 1,0 ml/phut do PA.

-

The tich tiem: 20 ul,

Da khao sat S\l' nrong quan giua nAng dQ dinh hrong voi dien tich pie, dQ l~p lai va dQ dung nitro trong gioi han eho phep, Do paracetamol la mQt thanh phfu1 co 1)' l~ IOnnen tnroc khi do HPLC cho 4 thanh phfu1can lai phai loai bo bat ra khoi h6n hop. Voi chuang trinh nay, ngoai vien nang tren, chung ta co th€ ap dung cho cac che pham khac co chua til 2 den 4 thanh phfu1 tren (CA, BR, CM va PE). Dan gian han nua, kh6ng co paracetamol thi kh6ng cfu1phai chi€t tach khi chuan bi dung dich thir va dung dich chuan, Tuy nhien, tnroc khi ap dung cho mot che pham cu the khac ta phai khao sat anh huang cua ta duoc. Phuong phap nay co the (rug dung eho ca dinh tinh va dinh hrong. Qui trinh da duoc sir dung lam tieu chuan co

sa.

5.2. Phuong phap ph in tieh da ciu til'MeA
Voi cac thuoc da thanh phan, dinh hrong bang HPLC v§n la mot phuong phap t6i
iru,

cho k€t qua nhanh chong va chinh xac, tuy nhien phuong phap nay doi hoi phai co

thiet bi HPLC d~t tien, chi phi cho dung m6i kha t6n kern. Phuong phap tach rieng cac thanh phan va dinh hrong rieng re t6n nhieu thai gian va c6ng sire, ngiroi thuc hien phai ti€p xuc voi cac dung m6i htru cc dQc hai, Phuong phap MCA co nhieu
Uti

diem

nhir phan tich nhanh chong, chinh xac, ti€t kiem duoc thai gian, c6ng sue cilng nhu dung m6i, hoa chAt. D~c bi~t phuong phap rAt thuan lei khi ta phai phan tich hang loat m§u thu gfu1giong nhau. Ngay nay, su phat trien manh me cua khoa hoc ky thuat trong linh V\l'C thi€t dien til co kha nang canh tranh va thay th€ ky thu~t HPLC trong met s6 twang hop the. RAt nhieu diroc pham co chua til 2 - 4 thanh phan hdp thu quang c6 - 82 -

hi
C1,l

phan tich, ky thu~t phan tich quang ph6 UV - Vis MCA voi SlJ tro giup cua may tinh

the ap dung

_~._l_ _?1}_{!!!: _c;_~!!.,!g !i!!!:
cling c6 mQt s6 han ch6 nhdt dinh. .. Trong cac thu6c da thrum phfm,

..

...

.

.. -

._- .. ---_._----_-----

phirong phap phan tich da cAu tir MeA. Tuy nhien, trong thuc t6 phirong phap nay

tY

1~ph6i hop gitra cac duoc chAt trong mQt

cong thirc thuoc doi khi rAt khac nhau roy thuoc vao nbng dQ cua duoc chdt hay nbng dQ gay tac dung duoc ly mong muon, Vi du: vien nen Trivitamin (BI + B6 + B12) duoc ph6i hop thea chAt la kh6 c6 th~ thuc hi~n diroc. ,. Khi phan tich mot cong tlnrc thuoc bdt ky, neu mQt chdt nao do co

tY

1~nrong

irng 250: 250: 1 (mg), V&i tY Ie chenh lech den v~y, phan tich MeA cho ca ba

tY l~ nho

va

diroc coi nhu "tap chat" thi doi khi lai co anh lnrong kha 1&0,anh huong nay tang thea s6 hoat chAt duoc ph6i hop trong ch6 pham. Trong mot sb tnrong hop thi S\I anh htrong do du la nho cung khong th~ bo qua. Vi du: h6n hop chua ba thrum ph§n la Paracetamol, Aspirin va Cafein, cac tac gia cling chi ap dung phan tich MeA thrum cong tren cac thuec con moi va

tY Ie acid

Salixylic nho diroi 1%, con n6u ty Ie nay tren 1% thi khong th~ ap

dung phuong phap MeA. .. MQt di~u dang chu

y

ntta la: trong cac diroc pham d~u co ta diroc va cac chAt

bao quan, neu cac chAt nay cling co kha nang hAp thu quang thi viec phan tich bang MeA co th~ cling khong thuc hien diroc. Vi du: cac che phsm thuoc tiem co 4 thanh phcln Vitamin B 1; B2, B6 va PP co ty l~ ph6i hop gitra cac thanh phfin kha

ly luang

cho viec phan tich d6ng thai

b~g MeA, nhirng vi trong h6n hQP cac thanh ph~ nay con co mQt ta diroc la a1col benzylic va mot s6 chAt bao quan khac d~u co kha nang hAp thu quang, do do viec phan tich hang MeA la khong th~ thuc hien duoc . ... Ngoai ra, voi S\I xmi! hien cua cac he phan tan rfut va he phan tan long nhfim ph6i hop cac hoat chAt co tinh hoa tan rAt khac nhau trong mQt dang bao che,
~~~~~~~~~~~~~~~~

thich hop, Cac hoat chdt nhieu khi lai co tinh chdt hdp thu tir ngoai kha ki€n khac nhau trong cac dung moi khac nhau (acid hay kiem) lam cho viec phan tich MeA trong nhieu tnrong hQP cu th€ khong co tinh kha thi. Vi vay chung toi da: nghien CUu xay dung met s6 quy trinh phan tich dbng thai (khong qua chi~t tach) m{)t s5 hoat chdt trong cac thu6c c6 2 thanh ph~ bang phuong phap phan tich toan ph6 tren cac may quang ph6. Tir do irng dung cac quy trinh da xay dung d€ phan tich mot s6 mdu thuoc chua hai thrum phcln nay dang luu hanh tren thi tnrong trong ca mroc.

- 83 -

_~._!!..q!!_?7!..~!!_£~¥'1Jg___., __., __.. __. __.. __.. __.

...

.

..

.

--. _--. ---. ----------------.

5.2.1. Dil xay dung duoc phirong phap dinh Iuong d6ng thai paracetamol va ibuprofen trong vien nen han hop bAng phuong phap phan tich toan ph6, cho k~t qua

nhanh, don gian do khong phai chiet tach. Phuong phap 6n dinh, co dQ chinh xac (ham
lirong paracetamol la 329,69 ± 1,58 mg, ibuprofen lit 208,5 ± 1,46 mg voi rmrc tin c~y 95%) va dQ dung chAp nhan duoc

(ry Ie tim

thAy cua ibuprofen bien thien tir 97,2%

d~n 99,2% va paracetamol bien thien tit 100,1% d~n 101,2%).

Phuong phap da dugc trung tarn ki~m nghiem duoc pham va
hanh tren th] tnrong tai dia phuong.

my pham Lang

san

tri~n khai co k~t qua dS phan tfch mot s6 mdu thuoc chua 2 hoat chAt tren dang hru

5.2.2. Dil xay dung mQt qui trinh dinh hrong d6ng thai paracetamol va quinine sulfat trong vien nen Antigrip F bang phirong phap da cAu tir (MCA) tren may quang ph6 thong thirong, xir ly k~t qua bang phfut mem tv' xay dung. Da ti~n hanh so sanh k~t qua thu duoc voi phuong phap do quang ph6 hAp thu ill ngoai thong thtrong (tieu chu§n co sa) sau khi chiet tach tirng thanh phan, Phuong phap co
iru

diSm lit nhanh, chinh xac, it tbn hoa ch~t, dung moi, V6'i h6n

hop chi chua 2 thanh phfut tren chi cAn do dQ hAp thu

a 4 buoc

song da khao sat la co

thS thtrc hien ducc phep dinh hrong co k~t qua t61. Han ntra, phuong phap nay chi yeu cdu co sa kiem nghiem co may quang ph6 thong tlnrong khong diroc trang bj sfuI phdn mem phan tich MCA. 5.2.3. Phuong phap MCA dtroc sir dung tren phftn mem sfut co cua may Quang phd GBC Cintra 40

aa diroc irng dung co k~t qua d~ dinh hrong

d6ng thai paracetamol

va acid mefenamic trong ch~ pham Pamesic. Phtrong phap dinh hrong diroc ti~n hanh trong moi tnrong kiem NaOH O,IN, voi dai biroc song phan tich tir 220nm d~n 300mn. Phuong phap cho k~t qua chinh xac (sai s6 nrong dbi la 1,05 va 0,8%) va dang tin c~y (zy 1~thu h6i Ia 99,87 d~n 100,25%). Chung toi hy vong co thS sir dung phuong phap phan tich quang ph6 MeA d~ b6 sung them hoac thay th~ cho phirong phap HPLC phdn nay khong xen phu nhau qua nhieu,

a co

sa khong co thiet bi HPLC. D@c

bi~t voi cac thuoc han hop co chua cac thanh phfut hApthu quang va ph6 cua cac thanh

- 84 -

TAt ca d~u bromhexin maleat hydroclorid. Xay dung dircc phirong phap MCA dA dinh hrong d6ng thai paracetamol va acid sir dung phdn mem sin co cua may quang ph6 GBC Cintra 40. dc) chinh xac va tinh cr rmrc chAp nhdn diroc (xem phfut ban lu~ cr tren).._~~~... Ung d\lng phuong phap HPLC Chung tai da xay dung dircc chuang trinh dinh tinh va dinh IUQ'11g hoat chAt cac cho cac h6n hop thu6c sau: Paracetamol Paracetamol Paracetamol Paracetamol Paracetamol maleat (eM). cafein. Ung d\lng phuong phap quang pb6 UV-Vis va ibuprofen phirong phap phan tich toan ph6.. hydroclorid (PH) va clorphenylamin (PA) va cafein (CA).. (PA). _r • " .. dn ducc ung dung co ket qua d~ dinh hrong hai hoat ch~t tren trong che pham Pamesic.~ 6. pseudoephedrin hydroclorid... cho ket qua nhanh. Ephedrine hydrocIorid. ~_Q __. (PA) va acid mefenamic (AM). clorpheniramin dung.- - - - - -- .. (PA) (PA) va va ibuprofen (IBu). dan va quinine sulfat Da xay dung duoc phuong phap dinh hrong d6ng thoi paracetamol trong vien nen h6n hop b~g gian do khong phai chiet tach. » ap dung: xay dung phirong phap co thA ap dung diroc cho nhieu san phAm co cung thanh phdn hoat chat. DQ l~p lai: sai s6 nrong d6i (hoac dQ l~ch chuan nrong d6i) d~t Dc) dung: kha nang tim lai d~t 2: 98%.+ .__ . Da xay dung mQt qui trinh dinh IUQ'11g d6ng thoi paracetamol trong vien nen Antigrip quang ph3 thong thuong. _ ..2.85 - .. .1. quinine sulfat (QS). • 6. Kit luan .__ or - - - - . xu mefenamic F bing phirong phap phan tich da cdu tU (MCA) tren may Iy ket qua bing phdn mem nr xay dung. Paracetamol._!_ - va ki~n nehi . . Cac phirong phap nay d~u co th~ ap dung dA dinh hrong d6ng thoi cac heat chdt thay cho phuong phap HPLC.999. .._.. phenylpropanolamin va Cac chuang trinh tren d~u ducc danh gia v~ tinh tuyen tinh. KET LuAN vA DE NOHl 6. 6. Kha nang » >- s 2%.__- - . theophyllin va phenobarbital. voi h~ s6 tuyen tinh d~u dat r > 0.__. M6i phirong phap d~u bao dam cac yeu cAu sau: >- Dc) tuyen tinh: x§y dung duoc plurong trinh h6i quy.

86 - . cac bao cao hQi nghi hoc trong mroc va qU6c t~. tharn dinh la co gia tri khoa hQCva da: dtroc phep gioi thieu tren cac tap chi chuyen nganh nhir tap chi kiem nghiem thuoc.6. K~t qua nghien ciru cua chung toi la co gia tri thuc ti~n. MQt s6 khao irng dung de xay dung tieu chuan cho cua minh. ve duoc va hoa MQt s6 chuang trinh dircc nghien crru Ia de lam tieu chuan cho cac co chuang trinh dang diroc cac co san pham sa tham sa. ti€p tuc danh gia cac ket qua d~ d€ nghi dua mQt s6 chuyen lu~ vao diroc . Tiep tuc nghien ciru plnrong phap quang ph6 MCA de co the ap dung cho nhtrng cong thirc co tren 2 thanh ph§n hoat chdt. tap chi diroc hoc. da: ducc vien kiem nghiem va mQt s6 trung tam ki€m nghiem img dung de kiem tra chdt hrong thuoc dang hru hanh tren thi tnrong.3. rna rc)ng trong nhtrng de tai khac. Da hOM thanh theo muc tieu va dAy diI cac nQi dung nghien ctm da d€ ra rna h¢i d6ng bQ da phe duyet cho de tai. Banh gia chung va d@nghj Cac nghien ciru tren d€u da diroc cac chuyen gia v€ kiem nghiern kiem tra. Chung toi mong diroc ti€p TI)C nghien CUud~ hoan chinh va di~n Vi~t nam trong Iftn xudt ban t6i.

2002. Thbng ke irng dung trong cong tac diroc.. (1995). 6. Trftn Th~ Phuong. Til sach sau dai hoc. 7.Ky y~u cac cong trinh NCKH 1996-2000. D3 Thi Oanh. (2002) Tieu chuin co s6 vien nen Pi-antalvic. sa vien nen Dibulaxan. Duoc di~n Vi~t nam III. Nguyen Thanh Dat. Dinh hrong d6ng thai sulfadoxin va pyrimethamin trong vien nen Fansida bAng phtrong phap HPLC va phirong phap quang ph6 dao ham. Xi nghiep dtroc pham TW 2. . Tieu chufin co sa vien nen Lopenca.2002. (2001). 2. (2001)_ Nghien ctru dinh luong mQt sb thubc da thanh phAn co chua paracetamol bang phirong phap HPLC. (1997). Thai Phan Quynh Nhu.87- .CT Diroc VTYT Tra vinh. 10. KHAo Tiing Vi?t 1.Iy va sinh hoc. (2002). BQ Y t~. Tieu chuan co sa vien bao dirong Antigrip sa vi en nen Desilogen. Cong ty Duoc VTYT Ti~n giang. Trfu:tVi~t Hung. Be>y t&. Cong ty diroc TW Hu~. Tieu chuan co s6 vien nen Pasepan. Tieu chuen co F. Tieu chuan co mefenamic. The United Pharma.2001. Thong bao kiern nghiem. 9. sa vien nen Alaxan. Nghien ciru dinh hrong cac vitamin tan trong mroc va tan trong dAu trong thubc Multivitamin bang sAc Icy long hieu nang cao. 8. Xi nghiep duoc pham TW 5. TAl LIEU THAM . Tieu chuan co 17.Truong Dai hoc dtroc Hit nQi . Dang Trftn Phuang H6ng. sb 1-2002. sa vien nang acid sulfat. Thai Duy Thin.i!!_!!f_l!_~Jy_q_'!'__I~!!{l_q 7. Xi nghiep diroc pham TW 2.. 3. Tieu chuan co sa vien nen Decolgen. Cong ty duoc pham Hit tay. Nguyen Ti~n Khanh. 76-81. The United Pharma. . Trinh Van Quy. Tieu chuan co 12. 4. Xi nghiep sa vien nen Quinin 16. Tr. Vien ki~m nghiem. sb 4. T?p 7. Tap chi phan tich hoa. 5. (1999). tnrong dai hoc duoc Ha nQi.Phan tich duqc pham bang ky thuat quang ph6 UV-VIS MeA. Tieu chuan co 18. Thong tin khoa hoc cong nghe diroc. de tai c§p be>. Thai Phan Quynh Nhu. Xi nghiep duoc pham TW 2 (1999). Trinh Van Quy. 11._?_·_T. 14. 13. 15. lien hi~p duoc H?u giang. Tieu chuan co s6 vien nen Sedapa.

p.. R. Sribun. 11G 178-Analytical Abstracts. C. Pharmacopee Francaise X. M. phenylephrin maleate in pharmaceutical dosage forms. 237-243. 20. . 27. 880. Poppi.. May 2004. Journal of Chromatografic Sience. 24. Spectrophotometry. The United State Pharmacopeia XXVII-2004. V. British pharmacopeia 1998. 26. N-way PLS applied to Simultaneous Spectrophotometric determination of acetylsalicylic acid. 21_European pharmacopeia III 1997. 2001.2000. J (2004). The United State Pharmacopeia XXIV . The Japanese pharmacopeia XIII ~1996. Sirisuppanonnon. The International pharmacopeia III~1981. Pharmacopeia of the people's Republic of China 1997. p. pp. Tantishaiyakul. 25.C! _ Ti2ng mruc ngoai 19. Hamide Ceniuva and Tunce1 Ozden Determination (2002). Clarke's isolation and identification of Drug (2th Edition) 1996. 05G6-Analytical Abstracts.88- . 30. M. 23. Simultaneous High Performance Liquid Chromatographic HCl and chlorpheniramine 97-100. Sena. K. Poeaknapo. 22. paracetamol and caffein. (1998). 29. ISSN 0021-9665 Volume 40. February 2002. XIV ~2001. 28. P. Simultaneous determination of dextromethophan HBr and Bromhexine HCl in tablets by first derivative 1998.._?_·__'[_q!_!!fH_~!t_q~_~4. Number 2. 2000. Nouvember of paracetamol.

Thong tin khoa hoc cong nghe diroc. Dinh tfnh. The third Indochina Conference 9 on farmaceutical Sciences. Tap chi ki~m nghiem thu6c s6 4. Tr. Thai Phan Quynh Nhtr (2001). Nghien CUu dinh hrong paracetamol va ibuprofen trong thuoc chua 2 thanh phan. CONG B6 LItN QUAN DEN Dt TAl 1 Nguyen Thanh D~. Thai Duy Thin. bromhexin hydroclorid.ll-l4. Nghien ctiu dinh luong mot s6 thu6c da thanh phan c6 chua paracetamol bang phirong phap HPLC. Tap chi kiern nghiem thu6c so 4. Hoi nghi hoa hoc toan quoc tlnr IV. Thai Duy Thin (2003). Thai Duy Thin. 279-285. Thong tin khoa hoc cong nghe dirocTnrong D~ hoc diroc Ha noi. Tr. 19-21. (2003). 76-81. Research on application of HPLC and UV spectrophotometry for quantitative and qualitative analysis of some multicomponent farmaceuticals of paracetamol. Nguyen Tirong Vy. Tap chi Diroc hoc so 5. Thai Duy Thin. HQi nghi hoa hQCtoan quoc IAnthu IV. Tr. Bangkok. Phung Ngoc Quang (2004). 2 3 4 5 U Quang Thao. pp136-143. Bili Thu Hue. Hung. Thailand. Dtnb hrong dong thoi paracetamol va ibuprofen trong vien nen bang phuong phap phan tich loan phd. Thai phan Quynh Nhu (2003). 6 Thai Duy Thin va cac CS (2003). Tran Thi Thuy.19-21. Tap chi diroc hoc so 7. Tr. Nguyen Thi Thanh. Nguyen Thi Huang. 2003. Dinh tinh va dinh hrong d6ng thai paracetamol va quinine sulfat trong vien nen antigrip F bang phirong phap HPLC. clorpheniramin maleat. Nguyen Thanh Dat (2003). Tr. va cafein trong nang cotusin bang phtrong phap HPLC. 4-7. 99-105. Dinh luong dong thci paracetamol va acid mefenamic trong thu6c vien bang phirong phap HPLC. D6 Thi Oanh. Tran Vie. 10/2003. Dinh hrong paracetamol. Thai Duy Thin.8. PHl) Ll)C cAc CONG TRINH NGmtN Tieng Vift: coo Dt\. Thai Phan Quynh Nhu. Tr. TrAn The Phuong. .Thai Duy Thm. Tr. 10-2003. Hoang Van Dire (2003).Truong Dai hoc duoc Ha noi. Tieng nuoc ngoai: Thai Duy Thin. 7 Ian 8 Thai Duy Thin va cac CS. Vo Nbi Ha. Dinh tfnh va dinh luong d6ng thOi paracetamol va quinine sulfat trong vien nen antigrip F bang phtrong phap phan tfch da cau tir MCA. dinh Iunng paracetamol va quinine sulfat trong che' pham h6n hop chua 2 thanh phan. May 20-23. Thai Phan quynh Nhu (2004). pseudoephedrin hydroclorid.

11 12 . November 10-13. 62-67. Tr. Research on application of HPLC for quantitative and qualitative analysis of some multicornponent fannaceuticals. Quynh-Nhu Thai Phan (2005). phenylpropanolamin hydroclorid and paracetamol in cough and cold tablets by HPLC. P. Thin Thai Duy. Chlorpheniramine Maleate and Phenylpropanolamine Hydrochloride in Decolgen Tablets. Ho Chi Minh city.10 Thai Duy Thin. Study on simultaneous assay of Dextromethorphan hydrobromid. 10th ASIAN chemical congress 10/2003. Clorpheniramin maleat. 34-39. Thai Duy Thin (2005). Simultaneous HPLC Assay of Paracetamol. Revue phannaceutique (Vietnam Journal of Pharmacy) 2-2005. Nguyen Thanh Dat (2003). The fouth Indochina Conference on farmaceutical Sciences.

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