LC-MS/MS法测定人血浆中曲美他嗪的浓度及其药动学研究

目的:建立以高效液相色谱-电喷雾串联质谱法测定人血浆中曲美他嗪浓度的方法,并研究其在健康人体内的药动学。方法:色谱柱为Shimadzu Shim-pack VP-ODS,流动相为甲醇-0.2%甲酸(12∶88),流速为0.8 mL·min-1,柱温为室温;采用电喷雾离子源(ESI源),选择正离子监测(SIM)质荷比(m/z)为267.25(曲美他嗪,M+H]+)和338.05(法莫替丁,M+H]+)的正电荷的准分子离子峰。结果:曲美他嗪血药浓度在2～250 ng·mL-1范围内线性关系良好(r=0.997 8),方法的定量下限为2 ng·mL-1;日内、日间RSD均≤9.3%,提取回收率在71.1%～75.8%之间(RSD≤5.4%)。22名受试者单剂量口服盐酸曲美他嗪片40 mg后曲美他嗪的平均药动学参数分别为:cmax(156.2±24.4)μg·L-1、tmax(2.16±0.36)h、t1/2(5.44±0.75)h、AUC0～24(1 191±205)μg·h·L-1、AUC0～∞(1 260±212)μg·h·L-1。结论:本方法简便、准确、灵敏、专属性强,适用于人血浆中曲美他嗪浓度的测定及其药动学研究,对于评价盐酸曲美他嗪疗效和安全性有重要意义。

Determination of Trimetazidine in Human Plasma by LC-MS/MS and Its Pharmacokinetic Study

OBJECTIVE： To establish an LC-MS/MS method for the determination of trimetazidine in human plasma and to study the pharmacokinetics of trimetazidine in healthy volunteers. METHODS： The determination was carried on a Shimadzu Shim-pack VP-ODS（150 mm×4.6 mm, 5 μm） column with mobile phase consisted of methanol-0.2% formic acid （12：88） at a flow rate of 0.8 mL·min^-1. Mass spectrum condition was electrospray ionization （ESI） and SIM mode selected ion mass spectral （m/z） 267.25 （trimetazidine, M＋H]^＋） and 338.05 （famotidine, M＋H]^＋）. RESULTS： The linear range of trimetazidine was 2- 250 ng·mL^-1 （r=0.997 8）. The lower limit of quantification （LLOQ） for trimetazidine in plasma was 2 ng.mL ＇. The RSD of intra-day and inter-day were lower than 9.3%. The extraction recovery was 71.1%-75.8% （RSD≤5.4%）. Mean pharmacokinetic parameters of trimetazidine in 22 healthy volunteers after a single oral dose of trimetazidine tablets 40 mg were as follows： Cmax （156.2 ± 24.4）μg·L^-1, tmax （2.16 ± 0.36）h, t1/2（5.44 ± 0.75）h, AUC0-24（1 191 ± 205）μg·h·L^-1, AUC0-∞（1 260 ± 212）μg·h·L^-1. CONCLUSION： The method is simple, accurate, sensitive and specific for the determination and pharmacokinetic study of trimeta- zidine in human plasma. It is of significance to evaluate curative efficacy and safety of trimetazidine hydrochloride.