南京医科大学学报（自然科学版）2017，Vol.37Issue(8)：955-960,6.DOI:10.7655/NYDXBNS20170807
同时测定小鼠血浆中氯吡格雷及其代谢产物浓度的LC-MS/MS法及其药代动力学研究
Determination of clopidogrel and its metabolites in plasma by LC-MS/MS and its application in the pharmacokinetics study in mice
摘要
Abstract
Objective:To develop and validate a sensitive high performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of clopidogrel and its metabolites and subsequently to use it to investigate pharmacokinetic properties of clopidogrel in mice.Methods:Clopidogrel and its metabolites were determined at an electron spray ionization (ESI) source using multiple reaction monitoring (MRM) in positive ion mode after protein precipitation by acetonitrile,in which piroxicam was added as an internal standard.Chromatographic separation was achieved on a Poroshell 120 SB-C18 column (100×2.1 mm,2.7 μm,Agilent Technologies) using a mobile phase that consisted of both solvent A (0.1％ formic acid in water) and solvent B (0.1％ formic acid in acetonitrile) in a gradient elution manner.The pharmacokinetics of clopidogrel was investigated in mice receiving a single dose of clopidogrel (10 mg/kg) by gavage administration.Results:The simultaneous assay of clopidogrel and its metabolites achieved good linearity (r＞ 0.99) within the range of the spiked plasma concentrations.The recoveries were greater than 80％,and no significant matrix effect was found.The both intra-and inter-day RSDs were less than 15％,and the accuracy ranged from-2.40％ to 5.00％.The stability of the method was good.In addition,a series of pharmacokinetics parameters were obtained in mice after receiving a single oral dose of clopidogrel through this analytical method.Conclusion:The modified methodology was highly sensitive,accurate,and reproducible for the simultaneous determination of clopidogrel and its three major metabolites in mouse plasma and therefore,it was successfully applied in pharmacokinetic studies of clopidogrel in mice.关键词
氯吡格雷/LC-MS/MS/药代动力学/药物代谢Key words
clopidogrel/LC-MS/MS/pharmacokinetics/drug metabolism分类
医药卫生引用本文复制引用
张梦然,邰婷,米琼宇,吉金子,黄贝贝,贾雨萌,谢红光..同时测定小鼠血浆中氯吡格雷及其代谢产物浓度的LC-MS/MS法及其药代动力学研究[J].南京医科大学学报（自然科学版）,2017,37(8):955-960,6.基金项目
国家自然科学基金(81473286,81503144) （81473286,81503144）
