LC-MS-MS法评价2种苯磺酸氨氯地平片的生物等效性

Bioequivalence of 2 amlodipine besylate tablets by LC-MS-MS in healthy Chinese volunteers

目的建立LC-MS-MS法测定人血浆中苯磺酸氨氯地平的浓度,并进行2个制剂间的生物等效性评价。方法采用随机交叉、自身对照试验设计,18名健康志愿受试者口服苯磺酸氨氯地平片受试制剂和参比制剂各10mg,以HPLC-MS-MS法测定服药后120h内不同时间点的血药浓度,计算主要药物动力学参数,以方差分析法对主要参数进行均数的差别检验,以双单侧t检验进行生物等效性判定。结果受试者分别口服受试制剂和参比制剂后主要动力学参数AUC0～120,AUC0～∞,tmax,Cmax,t1/2分别为(194.68±52.97)g.h.L-1、(192.74±49.56)μg.h.L-1、(209.29±51.85)μg.h.L-1、(209.45±55.38)μg.h.L-1,(7.0±1.3)h和(7.0±1.0)h、(6.23±1.86)μg.L-1和(6.27±2.41)μg.L-1、(32.7±10.0)h和(32.6±4.5)h。受试制剂对参比制剂的相对生物利用度为(101.0%±9.6%)。结论受试制剂与参比制剂为生物等效制剂。

Objective To develop an LC-MS-MS method to determine the plasma concentration of amlodipine,and evaluate the bioequivalence between 2 formulations of amlodipine besylate tablets.Methods A cross-over,randomized study was performed in 18 healthy volunteers.Concentrations of amlodipine in the plasma were assayed by HPLC-MS-MS method after a single oral dose of 10 mg of the test or the reference tablets.The pharmacokinetic parameters were analyzed by two one-sided t tests to evaluate the bioequivalence of the 2 preparations.Results The main pharmacokinetic parameters AUC0～120,AUC0～∞,tmax,Cmax,and t1/2 of the test and reference preparations were as follows：（194.68±52.97）μg·h·L^-1 and（192.74±49.56）μg·h·L^-1;（209.29±51.85）μg·h·L^-1 and（209.45±55.38）μg·h·L^-1;（7.0±1.3）h and（7.0±1.0）h;（6.23±1.86）μg·L^-1 and（6.27±2.41）μg·L^-1;（32.7±10.0）h and（32.6±4.5）h.The relative bioavailability of amlodpine was（101.0%±9.6%）.Conclusion The test and the reference preparations are bioequivalent.