LC-MS法测定人血浆中瑞格列奈的浓度及其片剂的生物等效性研究

Determination of Repaglinide Concentration in Human Plasma and Bioequivalent Study of Its Tablets by LC-MS

目的:建立测定人血浆中瑞格列奈浓度的方法,评价国产与进口瑞格列奈片的生物等效性。方法:采用随机、单剂量、完全三交叉试验设计,空腹口服国产瑞格列奈片(规格:每片0.5mg(受试制剂1)、每片1mg(受试制剂2))与进口瑞格列奈片(参比制剂)4mg,分别于服药前及服药后各时间点采集血样,用液-质联用(LC-MS)法测定人血浆中瑞格列奈的浓度,并使用DAS软件拟合计算药动学参数及评价生物等效性。结果:24名男性健康志愿者单剂量口服受试制剂1、2与参比制剂瑞格列奈片4mg后的主要药动学参数分别为cma(x45.9±14.9)、(44.2±12.8)、(44.8±13.7)ng·mL-1,t1/(21.16±0.19)、(1.05±0.31)、(1.18±0.44)h,tmax(0.82±0.56)、(0.81±0.57)、(0.98±0.62)h,AUC0～6(h90.0±23.9)、(85.9±25.0)、(97.9±22.7)ng·h·mL-1;AUC0～∞(93.3±24.3)、(88.7±26.1)、(91.8±23.5)ng·h·mL-1。受试制剂1、2的相对生物利用度分别为(106.5±31.1)%、(100.9±30.6)%。结论:国产瑞格列奈片与进口瑞格列奈片具有生物等效性。

OBJECTIVE： To establish the method for the determination of repaglinide concentration in human plasma, and to evaluate the bioavailability of domestic and imported Repaglinide tablets in healthy volunteers. METHODS： In a randomized single-dose three-way crossover design, a single oral dose of domestic Repaglinide tablets（test preparation 1,0.5 mg per tablet）, domestic tablets（test preparation 2,1 mg per tablet） and imported Repaglinide tablets（reference preparation） 4 mg were given to 24 male healthy volunteers. The blood samples were collected at different time points before and after medication. The plasma concentration of repaglinide was determined by LC-MS and the pharmacokinetic parameters and bioavailability were calculated using DAS software. RESULTS： The main pharmacokinetic parameters of test preparation 1, preparation 2 and reference preparation in 24 male healthy volunteers were as follows： cmax（45.9±14.9）ng·mL-1, （44.2±12.8）ng·mL-1 vs.（44.8±13.7）ng·mL-1;t1/2（1.16±0.19）h, （1.05±0.31）h vs.（1.18±0.44）h,tmax（0.82±0.56） h,（0.81±0.57）h vs.（0.98±0.62）h;AUC0～6 h（90.0±23.9）ng·h·mL-1,（85.9±25.0）ng·h·mL-1 vs.（97.9±22.7）ng·h·mL-1;AUC0～∞（93.3±24.3）ng·h·mL-1,（88.7±26.1）ng·h·mL-1 vs.（91.8±23.5）ng·h·mL-1. The relative bioavailability of test preparations were （106.5±31.1）% and （100.9±30.6）%, respectively. CONCLUSION： The domestic and imported Repaglinide tablets are bioequivalent.