LC-MS/MS法研究辛伐他汀片在健康人体内的药代动力学及生物等效性

Pharmacokinetic and bioequivalence studies of simvastatin tablet in healthy volunteers by LC-MS/MS

目的:建立人体血浆中辛伐他汀的LC-MS/MS测定方法,研究辛伐他汀片在男性健康志愿者体内的药代动力学行为,评价其生物利用度和生物等效性。方法:20名健康成年男性志愿者采用随机分组、自身两周期双交叉对照试验设计,单剂量口服参比制剂辛伐他汀片40 mg后,用LC-MS/MS联用法测定血浆中药物浓度。结果:试验制剂和参比制剂的主要药代动力学参数:Tmax分别为1.8±1.3、2.10±1.00 h;Cmax分别为7.12±1.61、7.38±1.54μg.L-1;AUC(0-24)分别为30.50±11.25、30.17±10.21μg.L.h-1;t1/2分别为3.90±0.78、3.76±0.85 h。以AUC(0-24)计算的试验制剂的相对生物利用度为(101.2±7.8)%。结论:建立的分析方法准确灵敏,测得的数据可靠,统计学分析表明两种制剂生物等效。

AIM： To establish a LC-MS/MS method for determination of simvastatin in human plasma, and investigate the pharmacokinetics and bioequivalence of simvastatin tablet in Chinese healthy volunteers. METHODS： 20 male healthy volunteers were randomized to receive a single crossover oral dose of simvastatin reference tablet or domestic tablet. The concentration of simvastatin in plasma was determined by LC-MS/MS. RESULTS： The main pharmacokinetic parameters of test and reference simvastatin tablets were as following： Tmas： 1.8 ± 1.3,2.10 ± 1.00 h, Cmax： 7.12 ± 1.61, 7.38 ± 1.54 μg·L^-1 AUC（0-24）： 30.50 ± 11.25, 30.17 ± 10.21 μg·h·L^- 1, t 1/2 ： 3.90 ± 0.78,3.76 ± 0.85 h, respectively. F（0-24） was （101.2± 7.8）%. CONCLUSION： The assay method is shown to be sensitive and accurate giving reliable results. The test tablet was bioequivalent to the reference tablet.