Simultaneous Determination of Clopidogrel and Its Metabolites in Human Plasma by UPLC-MS/MS
10.6039/j.issn.1001-0408.2015.35.15
- VernacularTitle:UPLC-MS/MS法同时测定人血浆中氯吡格雷及其代谢物的浓度
- Author:
Zengxian SUN
;
Haidong WANG
;
Shanhong NI
;
Cong CHENG
;
Naifeng LIU
- Publication Type:Journal Article
- Keywords:
Clopidogrel;
Active metabolite;
Inactive metabolite;
UPLC-MS/MS;
Plasma concentration;
Pharmacokinetcs
- From:
China Pharmacy
2015;26(35):4942-4945
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To establish the method for the simultaneous determination of clopidogrel (CLO) and its active metabolites (CATM) and inactive metabolites (CCAM),and to conduct pharmacokinetic study. METHODS:The plasma sam-ple had been derivatized by 2-bromine-3′-methoxy acetophenone(MPB),and was precipitated by acetonitrile. Using carbam-azepine as internal standard,UPLC-MS/MS was adopted. The separation was performed on Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of water(containing 0.1% formic acid)-acetonitrile(containing 0.1% formic acid)using a gradient elution program at the flow rate of 0.50 ml/min. The ESI was equipped and quantitative analysis was operated in posi-tive ion and MRM mode. The mass transition ion-pairs were followed as m/z 322.1→211.8(CLO),m/z 504.1→155.0(the alkyl-ation derivatives of CATM,CATMD),m/z 308.3→198.0(CCAM),m/z 273.2→194.3(internal standard). RESULTS:The lin-ear calibration curves for CLO,CATMD and CCAM were obtained in the concentration range of 0.03-20.00 ng/ml,0.30-200.00 ng/ml and 10.00-10 000.00 ng/ml in plasma,respectively;intra-day and inter-day RSD for them were all less than 15%,and relative error(RE)ranged from -3.5% to 5.7%. Main pharmacokinetic parameters of CLO,CATMD and CCAM in 5 healthy volunteers after oral administration of CLO 300 mg were as follows:cmax were(7.89±5.46),(15.58±8.08),(8 023.33± 1 047.39)ng/ml;tmax were(1.25 ± 0.43),(1.25 ± 0.43),(1.67 ± 0.29)h;t1/2 were (2.31 ± 0.61),(0.64 ± 0.08),(6.53 ± 2.55)h;AUC0-t were(17.19±14.59),(21.39±9.58),(30 648.85±8 026.63)ng·h/ml. CONCLUSIONS:The established method is sensi-tive,rapid and convenient,which is suitable for pharmacokinetic study and plasma concentration determination of CLO and its metabolites.
