岩黄连总碱胶囊在健康受试者体内的药动学研究

目的:建立LC-MS/MS法测定人血浆中脱氢卡维丁的浓度,研究不同剂量岩黄连总碱胶囊在中国健康受试者多次给药后的药动学.方法:采用随机、开放、多剂量给药设计的方法.16名健康志愿者随机分为2个剂量组(2 400 mg和3 200 mg),男女各半,每组8例,分别多次口服岩黄连总碱胶囊,每日1次,连续7 d,第7天在给药...

Pharmacokinetics of Yanhuanglian total alkaloids capsules in healthy volunteers

OBJECTIVE To develop the LC-MS/MS method for the determination of dehydrocavidine in human plasma, and study pharmacokinetics of Yanhuanglian total alkaloids capsules at different doses with repeated oral administration in Chinese healthy volunteers.METHODS A randomized, open, multi-dose design was conducted. Sixteen healthy volunteers (with half males and half females) were randomized into two groups with eight cases in each (2 400 mg and 3 200 mg). The sixteen subjects were orally administrated with Yanhuanglian total alkaloids capsules, once a day for seven days. On the 7^th day, the blood samples were collected at different time points after administration. The separation of plasma was performed on an Agilent ZORBAX SB-C₁₈ column (3.0 mm×100 mm, 3.5 μm) after precipitated by acetonitrile with the mobile phase consisting of 0.2% formic acid (containing 1 mmol·L^-1 ammonium formate)-acetonitrile (30∶70, V/V). Dehydrocavidine and dextromethorphan (IS) were detected by the MS system with an electrospray ionization (ESI) interface in positive ion mode. Multiple reaction monitoring (MRM) was used to monitor precursor to product ion transition of m/z 350.3→334.3 for dehydrocavidine and m/z 272.2→171.3 for IS. Pharmacokinetic parameters were calculated by WinNonlin 8.0 software.RESULTS The linear range of dehydrocavidine was 0.015-3 ng·mL^-1. The lower limit of quantification was 0.015 ng·mL^-1. The indicators of method validation were in line with the requirements. The main pharmacokinetic parameters of dehydrocavidine after oral administration of multiple doses of 2 400 mg and 3 200 mg were as follows, t_max were (1.75±1.04) h and (2.06±0.98) h, t_1/2 were (31.59±17.32) h and (35.98±14.46) h, AUC_0-t were (2.637±0.504)ng·h·mL^-1 and (3.150±0.485) ng·h·mL^-1, AUC_0-∞ were (5.512±1.792) ng·h·mL^-1 and (7.649±3.306) ng·h·mL^-1, respectively.CONCLUSION The LC-MS/MS method is simple and sensitive, and can be successfully applied to the pharmacokinetic study of Yanhuanglian total alkaloids capsules in healthy Chinese volunteers.