3. USP. 34,
4. Sandie Lindsay, High Performance Liquid Chromatography, 2nd edition, 1994.
SUMMARY
A reversed-phase liquid chromatography method was developed for assay of beta carotene in soft capsule. The method was carried by using a LiChrospher 100 RP-J8 (250 x 4 mm; 5 /im) column and a mixture of acetonitrile and ethanol (1:1) as mobile phase. The flow rate of mobile phase is maintained at 1.0 ml per minute, injection volume: 20 fil, analyle was detected by a DAD detector set at 450 nm. The method was validated in specificity, linear range; accuracy, precision.
Validation results proved that the developed method was suitable for assay for beta carotene in soft capsule and used to determme beta carotene in Vinphalaf soft capsule.
DINH Ll/OTNG CAC DANG CLORPHENIRAMIN
DANG DI/OC sis DUNG TRONG CHE PHAM THUOC B A N G P H I / O N G PHAP HPLC TREN C 6 T sAc Kt CHON LOC D 6 | QUANG
LE DINH CHI Tru&ng Bqi hoc Duac Hd Noi 1. Bat vSn de
Clorpheniramin la mot hoat chit co hoat tinh khang Histamin hien dang duac su dung ddng then duoi dang hon hop racemic cua hai dong phan doi quang (dexclorpheniramin va levoclorpheniramin) va dang dexclorpheniramin tinh khiet. Tren thi truong Viet Nam, hai dang hoat chat nay dang duoc sii dung dpc lap hoac phoi hgp voi nhi8u hoat chat khac, song trong Dugc di^n Viet Nam vin chua co chuyen luan nao dua ra phuang phap chinh thong cho phep dinh lugng rieng mpt each dac hieu dexclorpheniramin trong che pham thuoc. Mpt phuang phap nhu vay phai cho phep tach rieng biet hai dong phan doi quang cua clorpheniramin, nho do dexclorpheniramin se dugc dinh lugng ma hoan toan khong bi anh huong boi sir co mat cua levoclorpheniramin. Nhiing nghien ciiu dS dugc cong b6 chung toi tim duac [2],[3] moi chi danh gid d6n kha nang tach hai dong phan d6i quang ciia clorpheniramin ma chua danh gia miic dp phu hgp khi ap dung tren ch8 pham, nhat la che pham da thanh phan, va dp dac hi8u khi phan tich dong phan doi quang ciia clorpheniramin trong dieu kien co mat cac hoat chat khac. Yeu cSu v6 dp dac hi6u da dugc chiing toi giai quyet trong mgt nghien Cliu da cong bo ve dinh tinh phan biet clorpheniramin racemic va dexclorpheniramin [I]. Trong nghien cuu nay, chiing toi thuc hien xay dung mgt quy trinh phan tich bang HPLC cho phep dinh lugng ca hai dang clorpheniramin hien dang dugc sii dung trong ch6 pham thuoc: dang clorpheniramm racemic va dang dexclorpheniramin.
LE THI HL/ONG HOA Vi^n Kiem nghiem thuoc Trung ucmg
2. Thirc nghiem
2.1. Thiet bi, diing cii, hda chdt vd chdt chudn 2.1.1. Hoa chdt, chdt chudn
- Acetonitril, isopropanol loai dung cho HPLC;
- Triethylamin, acid acetic bang loai tinh khiSt phan tich;
- Chat chuan clorpheniramin maleat ciia Vi?n Kiam nghiem thu6c Tmng uong (SKS: 0198032;
ham iugng 100,0 % tinh theo che pham khan; dp am 0,10%);
- Chat chuSn dexclorpheniramin maleat cua USP (Lot H0D199; ham lugng 99,9 % tinh theo nguyen trang).
2.1.2. Thietbi, dungcy
- May sac ky long hi6u nang cao Merck - Hitachi dugc trang bi detector UV-VIS;
- Can phan tich Sartorius ED224S co do chinh xac tai 0,1 mg;
- May do pH Metrohm 691;
- Cpt sac ky chpn Igc doi quang Cyclobond I 2000 (250 X 4,6 mm, 5 ^im) co chiia pha tinh la P-cyclodextrin;
- Cac thiet bi thi nghiem c£in thi6t khac (dung cy thiiy tinh chinh xac c4p A, may iSc sieu am, bo IQC dung moi...).
Cac thiet bi phan tich sii dung trong qua trinh nghien cuu deu dugc hi?u chuSn va sii dung theo diing cac quy dinh cua ISO/IEC 17025 va GLP
10 T?p chi KIEM NGHlfM THU6c - So 3.2012; T?p 10.(37)
2 2 DM tufngfphmmgphdp nghien ciru 2.2.1. Doi tUQTig nghien cdu
Cic ch^ ph4m c6 chiia dexclorpheniramin diing cho nghi€n ciiu dugc tap hgp trong Bang 1.
Bdi^ 1. Cdc che phdm chua clorpheniramin maleat racemic va dexclorpheniramin maleat da nghien ciru STT TinOuiSc Tlianh phan cong thuc Ham
luffng Mrs san xuat So dang ky Sdlo Ch£ phim chira clorpheniramin maleat racemic
1
2 3
4
5
M£ii nin Decolgen Forte PS Viln nin Clorpheniramin 4 ViSn n^n Detazofol
Thu6c b^t Euquunol
Siro Coje Chai 75 ml (hitm lin^g cic ho^t chit du^c tinh trSn 5 ml siro)
Clorpheniramin maleat Paracetamol Pseudoephediin hydroclorid Clorpheniramin maleat Clorpheniramin maleat Paracetamol Clorpheniramin maleat Paracetamol Euquinin (Quinin ethylcarbonat) Clorpheniramin maleat Dipotassium glycyrrhizinat Pseudoephediin hydroclorid Cafein anhydrous
.-.2mg 500 mg
30 mg 4mg 2mg 400 mg
1 mg 50 mg 100 mg 16,65 mg 68,325 mg 225 mg 104,175 mg
Cong ty UNITED PHARMA
•W^tNam CTCP Dugc H$u Giang CTCP Dirgfc phim nk Noi
C6ng ty C6 ph§n Dugc phlin2/9-NADYPHAR
Cdng ty Co phin Du^c phimTW3
VD-570I-08
VD-3743-07 VNA-4212-01
VD-3373-07
VD-11166-10 005111
110410 28220609
0830809
ISIO
Chi pham chira desclorpheniramin maleat 6
7
Vign n£n CMesfarnin VtSn uin Cedetamin
Dexcloipheniramin maleat Betamethason Dexclorpheniramin maleat Betamethason
2mg 0^25 mg
2mg 0,25 mg
C6ng ty Co ph4n Dupc Ddng Nai Cong ty CP Dugc phim Khanh Hoa
VD-7406-09 050110 VD-2454-07 461009 2.2.2. Phuang phdp nghien cuu
2.2.2.1. Di^u ki^n sSc k^
Tii kSt qud khdo sat thvrc nghifm khd nang tach hai d6ng phdn ddi quang cua clorpheniramin tren he thdng HPLC Sli dyng tr6n cdc cOt sic k^ ho^t quang gSn P-cyclodextrin, chiing toi da tim dugc cac diSu ki?n sdc ky cho phep tdch hodn toan levoclorpheniramin vd dexclorpheniramin, cy th6 bao g6m:
- C0t Cyclobond (250x4,6 mm. 5 fim), duy tii d 18°C trong qua trinh phan tich
- Pha dQng: acetonitril - dung dich acid acetic 1 % dieu chinh pH v6 4,1 bdng triethylamin (4 : 96)
- T6C do ddng: \,0 ml/phiit - ThS tich tiem: 20 n\
~ Detector UV: 265 mn
2.2.2.2. Chuin bi dung djch chudn vd dung djch thii Dung dich chudn: H6a tan chat chudn clorpheniraminmaleatracemichaydexclorpheauamin maleat trong pha dpng d8 thu dugc cdc dung dich c6 ndng dp chmh xac khodng 30 ^ig/ml vdi clorphemramin
maieat racemic hay 15 ^g/ml vdi dexclorpheniramin maleat. Lgc qua mang Igc 0,45 p,m tnrdc khi tiem sic ky.
- Dung dich thu:
+ ChS pham dang vien: Nghi8n viSn thdnh bgt min, phdn tan mpt lugng chinh xac bdt vi6n trong pha dpng, Idc si6u am khodng 5 phiit d6 qud trinh hoa tan hoat chdt diln ra triet de. Lgc qua gidy lpc. Pha loang dich Ipc nSu cdn bdng pha dOng dS thu dugc dung dich cd ndng dd clorpheniramin maleat hoac dexclorpheniramin maleat tuong duong vdi dung dich chuan. Lpc qua mdng lpc 0,45 )jm trude khi tiem sdcky.
+ Che phdm dang siro: Pha lodng trong pha dpng cho tdi khi thu dugc dung dich c6 ndng dp clorpheniramin maleat hoac dexclorpheniramin maleat tuong duong vdi dimg dich chuan. Lpc so bp dung djch thu dugc qua gidy lpc, sau dd Ipc dich lpc qua mdng lgc 0,45 \im truoc khi tiem sdc ky.
Tsp cfaf K I £ M N G H I $ M T H U 6 C - S6 3.2012; T|p 10.(37)
2.2.2.3. Danh gia kk qua
DiSu kien sdc ky chiing tdi sii dung cho phep tach rieng hai ddng phan doi quang levoclorpheniramin va dexclorpheniramin cua clorpheniramin racemic thanh 2 pic rieng biet. Vi vay, clorpheniramin racemic maleat dugc dinh lugng thong qua viec tinh tdng dien tich thu dugc ciia 2 pic levoclorpheniramin va dexclorpheniramin, va dexclorpheniramin maleat dugc dinh lugng thdng qua viec tinh dien tich cua pic dexclorpheniramin.
3. Kit qud vd bdn luan 3.1. Thdm ^nh quy trinh phdn tich 3.1.1 Do dgc hieu
Dg thdm dinh do dac hieu cua phuang phap, chiing tdi da chuan bi mgt hon hgp nen mau tu tao gdm cac hoat chdt hay dugc sii dung phdi hgp vdi clorpheniramin: paracetamol, pseudoephednn
hydroclorid, guaifenesin, kali glycyrrhizinat, betamethason, dextromethorphan hydrobromid, bromhexin hydroclorid, cafein. Ndng do ciia mdi hoat chdt trong hdn hgp n6n mdu tu tao khoang 20 pg/ml, rieng paracetamol Id 100 Mg/ml. K6t qud thu dugc khi so sanh sdc ky dd cua hdn hgp n^n mdu tu tao khdng chiia clorpheniramin maleat (Hinh I: A) va hdn hgp ndn mdu tu tao sau khi them clorpheniramin maleat (Hinh 1: B) cho thdy hai ddng phan doi quang ciia clorpheniramin maleat dugc tach hodn toan khdi nhau (Hinh 1: B,C,D) va tach hoan todn khdi cdc hoat ch§t cd mat trong ndn miu tu tao. Nhu vay, phucmg phap phdn tich chiing tdi lua chgn khdng bi anh hudng bdi cac hoat chdt hay dugc sii dung phdi hgp vdi clorpheniramin maleat trong cac che phdm da thanh phan, va cd dp dac hidu phu hgp cho viec dinh lugng clorpheniramin maleat trong cac ch6 phdm thudc, U ca che pham da thanh phdn.
JS^
Hinh 1. Sdc ky do cua dung dich nen mdu tir tao (A), dung dich nen mdu lu tgo co them clorpheniramin maleat racemic (B).
chdl doi chieu clorpheniramin maieat racemic (C) vd chdt doi chieu dexclorpheniramin maleat (D)
3.1.2. Do tuyen linh
Dp tuyen tinh ciia phuang phap dugc chiing tdi danh gia cho clorpheniramin maleat racemic ciing nhu cho dexclorpheniramin maleat. Vdi clorpheniramin maleat racemic, dp tuydn tinh dugc danh gid thdng qua quan he giira tdng dien tich pic thu dugc ciia hai ddng phan ddi quang levoclorpheniramin va dexclorpheniramin vdi ndng dp tuang ung ciia clorpheniramin maleat racemic. De khao sdt dp tuydn tinh, chiing tdi thiet l?p mdt day dung dich chuan clorpheniramin maleat racemic gdm 5 dung dich cd ndng dp tii 11,60 ng/ml den 58,00 ng/ml, va mpt day dung dich chudn dexclorpheniramin maleat gdm 5 dung dich cd ndng dp tu 5,21 |Jg/nil den 26,06 fig^ml, sau do tien hanh phan tich tren may HPLC theo cdc dieu kien d muc 2.2.2.1. Ket qua phan tich cua timg day dung djch chuan dugc trinh bay tai cdc Bang 2 va 3, Hinh 2 va 3.
Tap chi KIEM NGHIEM T H U O C - Sh 3.2012; T^p 10.(37)
Bdng 2 Quan he giita tdng dien tich pic levoclorpheniramin vd dexclorpheniramin v&i nong
do clorpheniramin maleat racemic
Bdng 3. Quan he giira dien tich pic dexclorpheniramin vd nong do dexclorpheniramin
maleat N6ng d$
clorpheniramiit maleat (fig /mi) T^ng difn tich 2 pic (mV.s)
11,6
110994 23,19
241863 34,79
355569 46,38
502079 58,00
625428
Piiinmg ttlnii iioi quy tuyin tinii: y = 11114x - i9482 H | $6 tirong quan : r = 0,9994
N i n g d $ dexciorpheniramin
maleat (fig /mi) Difn tich pic (mV.s)
5,21
53128 10,42
117802 15,63
173891 20,84
248836 26,06
308132 Phirong trinh hdi quy tuyin tinh: y = I2299x-11905
Hf s l tiroug quan hii q n y : r = 0,9992
12299X-11905 R^ = 0.9984
0 20 40 eo SG N 6 n g d 9 l l s x c l o r p h e n l r a i n i n maleat (mcg/ml) r4&ngd4 clorpheniramin maleat (mcgfml) . . . . ..
Hinh 3. Do thi bieu dien quan h? giiia dien tich pic Hinh 2. Dd thi biiu diin quan h? giira tong dien tich pic dexclorpheniramin vd nong do dexclorpheniramin maleat
levoclorpheniramin va dexclorpheniramin va nong dp clorpheniramin maleat racemic
Kdt qua thu dugc cho thdy, vdi cd clorphenh-amin maleat racemic (Bdng 2) ciing nhu dexclorpheniramin maleat (Bdng 3), trong khoang ndng dp da khao sdt, c6 su tuong quan tuydn tinh chat che giira dien tich pic vd ndng dg ho^t chdt, vdi h$ sd tuang quan tuySn tinh r = 0,9994 cho clorpheniramin maleat racemic va r = 0,9992 cho dexclorpheniramin maleat.
3.1.3. Do lgp lgi
DO lap lai cua phuong phap dugc danh gid thdng qua dp l|.p lai cua kdt qua tdng hdm lugng clorpheniramin maleat ciing nhu ciia rieng dexclorpheniramin maleat trong chd phdm thu dugc sau 6 ldn phan tich dgc lap (Bdng 4) trdn man vien nen clorpheniramin maleat 4 mg ciia Cdng ty CP Dugc Hdu Giang.
Bdng 4. Ket qud xdc dinh dg lgp lgi vai clorpheniramin maleat racemic vd dexclorpheniramin maleat Lirang
cun m&u lhi(g) 0,0261 0,0254 0,0291 0,0257 0,0273 0,0301
Tdng dien tich 2 pic cuu ctorphenlrumin
(mV.s) 318155 311347 357152 314097 331736 365418 Trung binh
RSD (•/.)
Hum lir^g clorpheniramin maleat (mg/vien) linh Iheo KLTB vien
3,99 4,01 4,02 4,00 3,98 3,98 4,00 0,5
Diin lichpic dexclorpheniramin
(mVs) 150824 149701 170765 150142 159428 175391
Ham lirprng dexclorpheniramin muleut (mg/vien) tinh theo KLTB vien
1,79 1,82 1.81 1,81 1.81 1,80 l,8t 0,7
Tjp clii KitM NGH1$M THU6c - S6 3.2012; T4p 10.(37)
Nhu vay, danh gia tii\rc nghiem cho thdy phuang phap da thidt ldp co dO ldp lai tdt vdi ciorpheniramir maleat racemic (RSD = 0,5 %) vd dexclorpheniramin maleat (RSD = 0,7 %).
3.1.4. Do chinhxdc trunggian
Dp chinh xdc trung gian ciia phuang phdp dugc xac dinh khi dp dung dinh lugng clorpheniramin maleat racemic va dexclorpheniramin maleat bdng each so sanh ket qua 6 lan phan tich danh gia dd l^p Iai vdi 3 lan phan tich dgc lap duac thuc hien khac ngdy tren ciing mau chd pham vien ndn clorpheniramin maleat 4 mg cua Cdng ty CP Dugc Hau Giang. Qua 9 ldn phan tich thuc nghiem, vdi clorpheniramin maleat racemic (RSD
= 0,4 %) va dexclorpheniramin maleat (RSD = 0,9 %), phuang phap ddu thd hien dp chinh xac trung gian tdt (Bang 5).
Bdng 5. Kit qud ddnh gid do chinh xdc trung gian vai clorpheniramin maleat vd dexclorpheniramin maleat
Licfmg cSn thu(g)
Tong difn u'ch 2 pic ciia clorpheniramin
(mV.s)
Ham tirfmg clorpheniramin maleat (mg/viSn) linh Iheo KLTB vien
Difn lich pic dexclorpheniramin
(mV.s)
Ham lirfmg dexclorpheniramin maleat (mg/viert) tinh theo KLTB
vien
Ket qua d^nh gia d$ l^p lai 0,0261
0,0254 0,Ci291 0,0257 0,0273 0,0301
318155 311347 357152 314097 331736 365418 TVung binh
3,99 4,01 4,02 4,00 3,98 3,98 3,997; n = 6; RSD = 0,41 %
150824 149701 170765 150142 159428 175391
1,79 1,82 1,81 1,81 1,81 1,80 1,807; n = 6; RSD = 0,57%
Ket qua phan tich d$c iSp Ichac ngiy 0,0271
0,0266 0,0252
328057 325307 307019 Trung binh
RSD (%)
3,98 4,02 4,00 4,00 0,4%; n = 9
158023 157662 149377
1,81 1,84 1,84 1,82 0,9%; n = 9
3.1.5. Do dung
Dp diing ciia phuong phap dugc chung tdi tham dinh bdng each Uiem chinh xac chdt chudn clorpheniramin maleat racemic hoac chuan dexclorpheniramin maleat vao ndn mdu tu tao khdng cd clorphenhamin maleat ((B su dung dd tham dinh dp dac hieu) ya kidm ha lugng tim lai dugc ciia dang hoat chit cdn danh gia dd diing so vai lugng chat chuan cho vao ban dau.
Qua trinh tham dinh do diing dugc thuc hien d ba miic ndng dp vdi mdi dang hoat chdt. Voi clorphenirafflB maleat racemic, ba miic chudn them vao ndn miu tu tao ldn lugt la 232,0; 463,8; va 927,6 jig. V^ , dexclorpheniramin maleat, ba miic chudn them vao ndn mdu tu tao ldn lugt Id 104,2; 208,4; vd 416,8 ^%. ^ qua xac dinh Iugng tim lai vdi clorpheniramin maleat racemic va dexclorpheniramin maleat dugc trinh b^* i Bang 6 va 7.
Tap chi KIEM NGHI$M THUOC - So 3.2012; Tdp 1
Bdng 6. Kit qud ddnh gid do dung khi dinh Itrong clorpheniramin maleat Ltr^ng chuin clorpheniramin
maleat racemic thim vdo nen mdu IflfO (pg)
927,6
463,8
232,0
STT
1 2 3 1 2 3 1 2 3
TSng difn lich 2 pic cdu clorpheniramin
(mV.a) 499759 507596 500846 238172 240534 238516 111582 111252 111068
Lir0tg chuin clorpheniramin maleat tim Iffi
(m)
934,2 948,2 936,0 464,0 468,2 464,6 236,4 235,8 235,4
Tylf Um tal
(%)
100.7 102,2 100,9 100,0 100,9 100,2 101,9 101,6 101,5 Bdng 7. Kit qua danh gid do dung khi dinh Itt^g dexclorpheniramin maleat Lirtfng chuin dexclorpheniramin
maleat thim vdo nin muu tif t^o (fig)
416,8
208,4
104,2
STT
1 2 3 1 2 3 1 2 3
Difn lich pic dexclophenirumin (mK!)
242506 248785 243672 114940 117660 116524 52684 52129 52497
Lufmg chuin dexclorpheniramin maleat lim l^i
(fS) 413,6 423,8 415,4 206,4 210,8 209,0 105,4 104,4 105,0
Tyli lim lai
(•/.)
99,2 101,7 99,7 99,1 101,2 100,3 101,1 100,2 100,8 Ket qua trinh bdy trong cac Bdng 6 va 7 cho thdy ty Id thu hdi vdi cd clorpheniramin maleat racemic (100,0 % ddn 102,2 %) va dexclorpheniramin maleat (99,1 % den 101,7 %) deu tot. Nhu vay phuang phap cho dg diing tdt khi ap dvmg djnh lugng clorpheniramin maleat racemic ho|c dexclorpheniramin maleat.
3.2. uhg dung ^nh lupng clorpheniramin maleat, dexclorpheniramin maleat trong mpt so che phdm thudc Phuang phdp phan tich sau khi thdm dinh da dugc chiing tdi ung d^ng dinh lugng clorpheniramin maleat vd dexclorpheniramin maleat trong mOt sd chd phdm thudc (danh sdch d Bdng 1). Kdt qua thu dugc tren 5 chd phdm chiia clorpheniramin maleat racemic (Bang 8) va 2 chd phdm chiia dexclorpheniramin maleat (Bang 9) cho thdy vdi 5 che phdm chiia clorpheniramin maleat, tdng ham lugng xac dinh dugc ciia hai ddng phdn levoclorpheniramin maleat va dexcloipheniramin maleat dao ddng trong khodng tir 100,0 % ddn 101,1 % so vdi hdm lugng tren nhdn tuong iing, cdn vdi hai chd phdm chiia dexclorpheniramin maleat, hdm lugng xdc djr± dugc deu bdng 99,5 % ham Iugng tren nhdn. Nhu vdy, ham lugng clorpheniramin maleat h-ong cdc chd pham dugc khdo sdt ddu phii hgp vdi hdm lugng trdn nhdn.
Tap cbi KlfeM NGHI$M THU6c - S6 3.2012; Tfip 10.(37)
STT
1 2 3
»
5
Bdng 8. Kit qud xdc dinh hdm luang clorpheniramin maleat trong che pham
Tin thuoc
Decolgen Forte FS Clorpheniramin 4 Detazofol Euquimol Coje syrup (chai 75 ml)
Hum lirf/ng clorpheniramin maleal (mg/v)
2,02 4,00 2,01 1,00 16.66/5 ml
So v^ trin nhdn
(%)
101,1 100,0 100,6 100,0 100,1 Bdng 9. Kit qud xdc dinh hdm lucmg dexclorpheniramin maleat trong chi phdm STT
1 2
Ten thuoc
Cedesfarnin Cedetamin
Ham lirgmg dexciorpheniramin mateat (mg/viin)
1,99 1,99
So vai trin nhan
(%>
99,5%
99,5%
4. Kdt ludn
Quy trinh phdn tich ddng phan ddi quang ciia clorpheniramin maleat bang phuong phap HPLC sii dyng cdt sac ky hoat quang gan p-cyclodextrin da dugc iing dung dd dinh lugng clorpheniramin maleat racemic va dexclorpheniramin maleat trong che pham thudc. Kdt qud thdm dinh cho thdy quy trinh cho phep dinh tinh phan biet mdt each dac hieu hai dang clorpheniramin maleat kd trdn trong che pham thudc, ke ca ch6 phdm da thanh phan. Quy trinh da dugc iing dung dinh lugng clorpheniramin maleat racemic va dexclorpheniramin maleat trong 7 che pham thudc, ket qua danh gia cho thdy ham lugng hoat chat xac dinh dugc trong cac ch6 pham nay hoan toan phii hgp vai ham lugng ghi tren nhan.
Tai lidu tham khao
I. Le Dinh Chi, Le Thi Huong Hoa, Tap chi Kiim nghiem, s6 1 (tap 10 - s6 35), tr. 18 - 22, 2012.
2 K.M. Fried, A E.Young, S.U.Yasuda, I. W. Warner, Journal of Pharmaceutical and Biomedical Analysis, 27, tr. 479-488, 2002.
3. T.Cleveland, Joumal of Liquid Chromatography, IS (4), tr. 649 - 671, 1995.
SUMMARY
A chiral HPLC method was developed for assay of chlorpheniramine maleate racemic and dexchlorpheniramme maleate. the two forms currently used in pharmaceutical products. The detailed HPLC conditions are as follow:
- Chiral column Cyclobond (250 x 4.6 mm. 5 pm). maintained at 18°C during analysis.
- Mobile phase, acetonitrile -1% solution of acetic acid. pH adjusted to 4.1 with triethylamine (4 : 96) - Flow rate- 1.0 ml/min
- Injection volume • 20 pi - UV detector setal265nm
The method was validated on its specificity, precision, intermediate precision, accuracy and linearity, proving its suitability for assay of chlorpheniramine maleate racemic and dexclorpheniramine maleate in pharmaceutical products, even in multi active ingredients formulation.
Tap chi KIEM NGHIEM THUOC - So 3.2012; T|p 10.{37)
