【摘要】 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。更多还原

【Abstract】 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,5μm)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-1.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 trimetazidine in human plasma.It is of significance to evaluate curative efficacy and safety of trimetazidine hydrochloride.更多还原