液相色谱-质谱法测定人血浆中阿折地平的浓度及其药动学

目的：建立阿折地平血药浓度的液相色谱-质谱(LC-MS)测定法,进行人体药动学研究。方法：采用LC-MS法,测定16名健康受试者口服受试制剂(单剂量含阿折地平8,16 mg和多剂量)后血浆中阿折地平浓度。结果：口服受试制剂(单剂量8,16 mg)后,估算的阿折地平的药动学参数分别为：t_(1/2β)为(22．8±s 2．4),(24±4)h；t_(max)为(2．8±1．2),(3．0±0．9)h；c_(max)为(8．7±1．2),(19±4)μg·L~(-1)；V_d为(1749±964),(2480±2212)L；AUC_(0～96)为(186±47),(429±145)μg·h·L~(-1)；MRT为(25．7±1.3),(26．2±2．2)h。多剂量口服受试制剂(8mg,qd×7 d)血药浓度达稳态后估算的阿折地平的药动学参数c_(ss max)为(15．0±2．3)μg·L~(-1),t_(max)为(2.4±0．9)h,c_(ss min)为(3．8±0．9)μg·L~(-1),c_(av)为(7．0±1．5)μg·L~(-1),DF为(1．6±0．3),AUC_(ss)为(169±37)μg·h·L~(-1)。结论：本方法结果准确,灵敏度高,阿折地平在大部分人体内的过程符合二室开放模型,其主要药动学参数与国外文献报道数据一致,可为临床给药方案提供参考。

Determination of azelnidipine in human plasma by LC-MS and study on its pharmacokinetics

AIM:To establish a LC-MS method to study the pharmacokinetics of azelnidipine tablet in 16 Chinese healthy volunteers.METHODS:Sixteen healthy volunteers received tested tablet for each of a single oral dose of azelnidipine 8,16 mg and multidose.Drug concentrations in plasma were determined by LC-MS. RESULTS:The main pharmacokinetic parameters of single oral doses (8mg,16mg) were as follow:t_(1/2β)(22.8±s 2.4),(24±44) h;t_(max)(2.8±1.2),(3.0±0.9) h;c_(max) (8.7±1.2),(19±4)μg·L~(-1);V_d (1749±964),(2480±2212)L;AUC_(0-96)(186±47),(429±145)μg·h·L~(-1);MRT (25.7±1.3),(26.2±2.2)h.The main pharmacokinetic parameters of multidose were as follow:C_(ss max)(15.0±2.3)μg·L~(-1);t_(max)(2.4±0.9)h;c_(ss max)(3.8±0.9)μg·L~(-1),C_(av)(7.0±1.5)μg·L~(-1);DF (1.6±0.3);AUC_(ss) (169±37)μg·h·L~(-1). CONCLUSION:The method is accurate,sensitive and reliable,coincided with a two-compartment open pharmcokinetics model for azelnidipine plasma concentration-time data analysis.The main pharmacokinetic pa- rameters of the domestic azelnidipine tablet were similar to those reported abroad,providing information for clin- ical application.