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目的:建立恒河猴血浆中巴替非班浓度的高效液相-串联质谱(Liquid Chromatography-TandemMass Spectrometry,LC-MS/MS)测定法,并研究其在恒河猴体内的药代动力学。方法:取恒河猴血浆200μL,加入含2μg.mL-1内标依替巴肽的乙腈-甲醇(70∶30)混合溶剂600μL沉淀蛋白,取上清液吹干,残留物加100μL流动相复溶,取上清液进行LC-MS/MS分析。色谱柱为ODS C18柱(150 mm×4.6 mm,5μm),流动相为甲醇-20 mmol.L-1甲酸铵(50∶50),流速为0.4 mL.min-1;质谱采用电喷雾离子化,正离子检测,巴替非班和内标的选择性检测离子分别为m/z 818.3→632.4和m/z 832.0→646.2。结果:巴替非班的线性范围为25～5 000 ng.mL-1,最低定量下限(lower limit of quantitation,LLOQ)为25 ng.mL-1,准确度、精密度及回收率均符合要求。结论:本方法专属性强,检测限低,灵敏度高,线性关系良好,方法简便快捷,适用于巴替非班临床前药代动力学研究。
OBJECTIVE: To establish a LC-MS / MS method for the determination of spandex in plasma of Rhesus macaques and study its pharmacokinetics in rhesus monkeys. Methods: 200μL of rhesus monkey plasma was added to 600μL of acetonitrile-methanol (70:30) mixed solvent containing 2μg.mL-1 internal standard etidirol to precipitate the protein. The supernatant was evaporated to dryness. The residue was added with 100μL of mobile phase Re-dissolved, the supernatant for LC-MS / MS analysis. The column was ODS C18 column (150 mm × 4.6 mm, 5 μm) and the mobile phase consisted of methanol-20 mmol.L-1 ammonium formate (50:50) at a flow rate of 0.4 mL · min-1. , Positive ion detection, selective test banzafiban and internal standard ions were m / z 818.3 → 632.4 and m / z 832.0 → 646.2. Results: The calibration curve was linear over the range of 25 to 5 000 ng.mL-1 with a minimum limit of quantitation (LLOQ) of 25 ng.mL-1, and the accuracy, precision and recovery were satisfactory . Conclusion: The method has the advantages of high specificity, low detection limit, high sensitivity and good linearity. The method is simple and rapid and is suitable for the preclinical pharmacokinetics study of batipy.