液相色谱-串联质谱法测定人血浆中的氯吡格雷

Determination of Clopidogrel in Human Plasma by LC-MS /MS

目的：建立灵敏、快速液相色谱-串联质谱法测定人血浆中氯吡格雷的浓度,并用于人体药动学研究.方法：500μl的血浆样品经甲基叔丁基醚提取处理后,以0.4％甲酸-乙腈（30∶70）为流动相,Poroshell 120 SB-C18柱分离,通过电喷雾离子源四极杆串联质谱,以多反应监测方式进行检测,选择离子反应为m/z 322.0→212.1（氯吡格雷）和m/z285.0→193.1（地西沣）.结果：氯吡格雷在5.04～10 080.0 pg/ml浓度范围内线性关系良好,定量下限为5.04 pg/ml,日内、日间精密度均不大于13.6％,氯吡格雷和内标地西泮的回收率分别为86.4％～ 88.6％和91.4％～100.2％.结论：该法选择性强、灵敏度高,适用于氯吡格雷片的临床药代动力学研究.

Objective： To establish an LC-MS/MS method for the determination of clopidogrel in human plasma, and was used for the pharmacokinetics investigat in human. Methods： Plasma samples treated with methyl tea-butyl ether （MTBE） extraction were separated on poroshell 120 SB-C18 column with a mobile phase of formic 0.4% acid-Methyl Cyanides （30 ： 70）. The detec- tion was carried out by means of electro spray ionization mass spectrometry in positive ion mode. Multiple reaction monitoring （MRM） mode was used with the transitions of m/z 322.0-212. 1 for clopidogrel and m/z 285.0---193. I for internal standard, re- spectiyely. Results： The calibration curve of c!opidogrel was linear in the range of 5. 04 - 10 080. 0 pg/ml. The limit of quantifica- tion was 5.04 pg/ml. The .extraction recovery of clopidogrel was 86.4 % -88. 6%, and that of internal standard was 91.4% - 100. 2%. The RSD of intra-and inter-day were less than 13.6%. Conclusion： The method is shown to be simple, accurate, sensi- tive and specific for the determination of clopidogrel in human plasma.