液相色谱-质谱-质谱联用法测定人血浆中氨氯地平

DETERMINATION OF AMLODIPINE IN HUMAN PLASMA BY LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY

目的 建立测定人血浆中氨氯地平的液相色谱 质谱 质谱联用法。方法 血浆样品经液 液萃取后 ,以乙腈 水 甲酸 (75∶35∶1)为流动相 ,采用ZorbaxC8柱分离 ,通过电喷雾离子化四极串联质谱 ,以选择离子反应监测(SRM )方式进行检测。用于定量分析的二级碎片离子分别为m/z 2 38(氨氯地平 )和m/z 116 (内标 4′ 羟基普罗帕酮 )。结果 线性范围为 0 4- 16 0ng·mL-1,最低定量浓度为 0 4ng·mL-1,每个样品测试时间仅 3 7min。在氨氯地平临床药物动力学研究项目中 ,应用此法可在两周内测试 15 0 0多个血浆样品。结论 该法灵敏度高 ,操作简便 ,快速、准确 ,适用于临床药物动力学研究。

AIM To develop a sensitive and specific LC/MS/MS method for determination of amlodipine in human plasma. METHODS Amlodipine and internal standard 4′ hydroxypropafenone were extracted from plasma using liquid liquid extraction, then separated on a Zorbax C 8 column. The mobile phase consisted of acetonitrile water formic acid (75∶35∶1), at a flow rate of 0 4 mL·min -1 . A Finnigan TSQ tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor → product ion combinations of m/z 409 → 238 and m/z 358 → 116 was used to quantify amlodipine and internal standard, respectively. RESULTS The linear calibration curves were obtained in the concentration range of 0 4-16 0 ng·mL -1 . The limit of quantification was 0 4 ng·mL -1 . Each plasma sample was chromatographed within 3 7 min. The method was successfully used in several pharmacokinetic studies for amlodipine. More than 1 500 plasma samples were assayed within two weeks. CONCLUSION The method is proved to be suitable for clinical investigation of amlodipine pharmacokinetics, which offers advantages of specificity, speed, and greater sensitivity over the previously reported methods.