目的建立液相色谱-质谱联用法(HPLC-MS/MS)测定人血浆中氯吡格雷的血药浓度。方法以硫酸氢氯吡格雷-d4作为内标,色谱柱为Xterra~RP_(18)(4.6 mm×100 mm,3.5μm),流动相为乙腈∶水相(0.1%甲酸水溶液)=66∶34,流速为1.0 m L·min~(-1)。三重四极杆质谱仪进行多反应监测模式,电喷雾离子源正离子检测。生物样品预处理用乙腈直接沉淀蛋白。考察该方法的专属性、标准曲线和定量下限、精密度与回收率、稳定性、溶血实验及试验样品再分析实验。结果线性范围为5.00~5000.00 ng·L~(-1),最低定量下限为5.00ng·L~(-1);批内、批间精密度均在1.28%~9.86%,相对偏差(RE)在-6.19%~14.27%;低、中、高3种浓度氯吡格雷质控样本内标归一化的基质效应分别为(113.69±10.62)%,(104.96±5.23)%,(105.12±4.01)%;提取回收率分别为(103.07±5.75)%,(102.87±14.34)%,(97.76±2.04)%。采血时溶血不影响测定准确度;试验样品再分析实验准确度符合要求。结论本方法是一种特异、快速、灵敏、稳定的HPLC-MS/MS,适用于人血浆中氯吡格雷的检测和药代动力学研究。 Objective To establish a HPLC-MS / MS method for the determination of clopidogrel in human plasma. Methods Clopidogrel bisulfate-d4 was used as internal standard. The chromatographic column was Xterra ~ RP_ (18) (4.6 mm × 100 mm, 3.5 μm). The mobile phase consisted of acetonitrile: water (0.1% 34, the flow rate is 1.0 m L · min ~ (-1). Triple quadrupole mass spectrometer multi-reaction monitoring mode, electrospray ionization positive ion detection. Biological Sample Pretreatment Protein is precipitated directly with acetonitrile. The specificity, standard curve and lower limit of quantitation, precision and recovery, stability, hemolysis and reanalysis of test samples were investigated. The results showed that the linear range was 5.00 ~ 5000.00 ng · L -1, the lowest limit of quantification was 5.00 ng · L -1. The intra- and inter-batch precision were 1.28% -9.86%, and the relative deviation (RE) (-6.39 ± 10.62)%, (104.96 ± 5.23)%, (105.12 ± 4.01)%, respectively. The normalized matrix effects of internal standard of low, medium and high concentrations of clopidogrel were ) Respectively. The recoveries were (103.07 ± 5.75)%, (102.87 ± 14.34)% and (97.76 ± 2.04)%, respectively. Blood hemolysis does not affect the accuracy of determination; re-analysis of experimental samples to meet the accuracy requirements. Conclusion This method is a specific, rapid, sensitive and stable HPLC-MS / MS for the detection and pharmacokinetics of clopidogrel in human plasma.