复方甘草酸苷胶囊的生物等效性研究

目的建立人血浆中甘草酸苷的代谢产物——甘草次酸的高效液相色谱-质谱测定法,并评价2种制剂的人体生物等效性。方法 18例男性健康受试者随机分成2组,分别交叉口服复方甘草酸苷胶囊4粒(含甘草酸苷100mg)和复方甘草酸苷片4片(含甘草酸苷100 mg)后,采用HPLC-MS法测定人血浆中甘草次酸的浓度。结果血浆中甘草次酸的最低定量限为5 ng.mL-1,在5~500 ng.mL-1与峰面积线性关系良好。提取回收率为70.2%~82.2%。受试制剂与参比制剂的各主要药动学参数:t1/2分别为(11.25±3.02)和(11.61±2.55)h,Cmax为(376.0±77.1)和(356.8±69.6)ng.mL-1,tmax为(11.56±2.43)和(10.22±2.98)h,AUC0-t为(5 742±1 689)和(5 882±1 645)ng.h.mL-1。结论本方法灵敏、准确、简便,适用于临床药动学及生物等效性研究;两种制剂具有生物等效性。

Bioequivalence of glycyrrhizin capsules by HPLC-MS

Objective To develop an HPLC-MS method for the determination of glycyrrhetic acid in human plasma and to estimate the bioequivalence of glycyrrhetic acid in healthy volunteers.Methods A single oral dose of glycyrrhizin capsules and tablets was given to 18 healthy volunteers in a two-way crossover design to study the bioequivalence.Glycyrrhetic acid concentrations in the plasma were determined by HPLC-MS.Results Calibration curve of glycyrrhetic acid was linear over 5-500 ng·mL^-1,the limit of quantitation for glycyrrhetic acid in the plasma was 5 ng·mL^-1,and the recovery was 70.2%-82.2%.The main pharmacokinetic parameters of the test capsules and reference tablets were as follows： t1/2 was（11.25 ± 3.02）and（11.61±2.55）h,Cmax was（376.0±77.1）and（356.8 ± 69.6）ng·mL^-1,tmax was（11.56±2.43）and（10.22±2.98）h,AUC0-t was（5 742±1 689）and（5 882±1 645）ng·h·mL^-1.Conclusion The method is sensitive,accurate,and convenient.It can be applied in the study of pharmacokinetics and bioequivalence of glycyrrhetic acid in humans.The two formulations are bioequivalent.