HPLC-MS/MS法测定人血浆中美普他酚的浓度

Determination of meptazinol in human plasma by HPLC-MS/MS

目的:建立人血浆中美普他酚浓度的HPLC-MS/MS测定法。方法:血浆样品500μL经液-液萃取后,以10 mmol.L-1醋酸铵(含0.5%甲酸水溶液)-乙腈(70∶30)为流动相,采用InertsilCN(150 mm×4.6 mm,3.5μm)柱分离,采用电喷雾电离化(ESI)方式和多反应离子监测(MRM)模式进行正离子检测。用于定量分析的离子反应分别为m/z 234.2→107.0(美普他酚)和m/z 152.0→110.0(对乙酰氨基酚)。结果:美普他酚血药浓度线性范围为0.20～508.00μg.L-1,定量下限为0.20μg.L-1。低、中、高3个浓度提取回收率分别为68.1%,67.0%,65.6%。结论:该法操作简便、快速、灵敏,适用于美普他酚的药代动力学研究及制剂的生物等效性评价。

Objective： To develop a high-performance liquid chromatography coupled to tandem mass spectrometry （HPLC-MS/MS） method for quantification of meptazinol in human plasma. Methods： After a simple liquid-liquid extraction, meptazinol and the internal standard paracetamol were separated on a Inertsil CN （150 mm ×4.6 mm, 3.5μm） column and detected by tandem mass spectrometry. The mobile phase consisted of 10 mmol·L^-1 ammonium acetate （including 0.5% formic acid water）-acetonitrile （70： 30）. A mass spectrometer equipped with electrospray ionization source was used as detector operated in the positive ion mode. Multiple reaction monitoring （MRM） mode was used with the trasitions of m/z 234.2→107.0 for meptazinol and m/z 152.0→110.0 for the internal standard, respectively. Results： The linear calibration curve was obtained in the concentration range of 0.20 - 508.00 μg· L^-1. The limit of quantification was 0.20 μg· L^-1. The extraction recoveries of the three concentrations were 68.1% , 67.0% and 65.6% , respectively. Conclusion： This method is proved to be suitable for the clinical investigation of meptazinol pharmacokinetics, which offers the advantages of specificity, speed and greater sensitivity compared with the reported methods.