血浆中硫普罗宁的测定及其片剂的人体生物等效性

Determination of tiopronin in human plasma and study on its bioequivalence

目的:建立人血浆中硫普罗宁浓度的LC-MS/MS测定方法,研究硫普罗宁在健康人体内的药动学行为,评价2种制剂的生物等效性。方法:20例健康志愿者交叉口服试验制剂硫普罗宁片剂或参比制剂硫普罗宁肠溶胶囊200mg,血药浓度-时间数据经DAS2.0统计软件处理,计算主要药动学参数,并对2种制剂进行等效性评价。结果:硫普罗宁在4.05～8100μg·L-1范围内线性关系良好,最低检测为4.05μg·L-1。方法回收率(n=5)为85.0%～91.3%,日内和日间精密度均小于15%。硫普罗宁片剂与肠溶胶囊的主要药动学参数分别是:Cmax为(2151.1±1135.0)μg·L-1和(2363.0±1055.1)μg·L-1;tmax分别为(4.8±1.3)h和(4.3±1.2)h;AUC(0-t)分别为(11618.2±3625.5)μg·h·L-1和(12824.0±4464.1)μg·h·L-1;AUC(0-∞)分别为(12677.7±3874.9)μg·h·L-1和(13803.1±4686.0)μg·h·L-1。结论:该法操作简单、灵敏度高、专属性强;统计学分析结果显示2种制剂具有生物等效性。

AIEglliACT..OI^ECI＇IVE To establish an UFLC MS/MS method for determination ot tiopronin in human plasma and investi- gating the pharmacokinetics and bioequivalence of tablets and enteric-coated capsules in healthy volunteers. METHODS Twenty volunteers were randomly divided into two groups（test and reference）in a double crossover design. Pharmacokinetic parameters were calculated with DAS 2. 0 program. RESULTS The linear range was 4. 05 - 8 100μg·L^-1 , and the limit of determination was 4. 05μg·L^-1. The method recoveries were 85.0%- 91.3% and the RSD of within-day and between-day was less than 15%. The main pharmacokinetic parameters of tiopronin tablets and enterosoluble capsules were as follows： Cmax （2 151. 1± 1 135.0） μg·L^-1 and （2363.0±1 055. 1）μg·L^-1;tmax（4.8± 1.3） hand （4.3 ± 1.2）h;AUC（0-t）（11 618.2±3625.5） μg·L^-1 and （12 824. 0 ± 4 464. 1）μg·h·L^-1 ; AUC（0 t） （12 677. 7 ± 3 874. 9） μg·h·L^-1 and （13 803. 1 ± 4 686. 0）μg·h·L^-11. CONCLUSION The method is simple, sensitive and specific and the statistical analysis showed that the test and reference preparation were bioequivalent.