苯磺酸氨氯地平片在健康人体内的药动学研究

目的：建立测定人血浆中氨氯地平浓度的LC-MS-MS法，并应用于健康人体药动学研究。方法：12例男性健康志愿者单剂量口服10mg苯磺酸氨氯地平片，血浆样品经液-液萃取后，用LC-MS-MS法测定血浆中氨氯地平浓度，采用非房室模型计算药动学参数。结果：本分析方法标准曲线线性范围为0．501～20．04ng／mL，最低定量浓度为0．501ng／mL。单剂量口服10mg苯磺酸氨氯地平片后，主要的药动学参数分别为cmax（9．57±1．08）ng／mL、tmax（5．92±0．79）h、t1/2（30．14±5．46）h、MRT（45．25±6．08）h、C1／F（40.02±4．98）L／h、AUC0～96（312．78±34．07）ng·h·mL^-1和AUC0—∞（352．09±42．45）ng·h·mL^-1。结论：本分析方法的准确度、灵敏度、重现性及线性范围等均符合生物样品的分析要求，适用于苯磺酸氨氯地平片的人体药动学研究。

Pharmacokineties of amlodipine besylate tablets in healthy volunteers

Objective： To develop a sensitive and specific LC-MS-MS method for determination of amlodipine in human plasma and investigate the pharmacokinetics of amlodipine besylate tablets in healthy volunteers. Methods： Twelve male healthy volunteers received single oral dose of amlodipine besylate tablets 10 mg. The plasma concentrations of amlodipine were determined by LC-MS-MS method after liquid-liquid extraction. The pharmacokinetic parameters were calculated by non-compartment model. Results： The calibration curve was linear in the concentration range of 0. 501-20.04 ng/mL. The limit of quantification was 0. 501 ng/mL. The method was successfully applied to pharmacokinetic study of amlodipine besylate tablets. The main pharmacokinetic parameters of amlodipine were as follows; cmax （9.57 ± 1.08） ng/mL, tmax （5. 92 ± 0. 79） h, t1/2 （30. 14± 5.46） h,MRT （45.25±6.08） h, C1/F （40.02±4.98） L/h,AUC0-96 （312. 78±34. 07） ng · h · mL^-1 and AUC0-∞ （352.09± 42. 45） ng · h · mL^-1. Conclusion：The method is proved to be accurate, sensitive, linear and reproducible for the determination of amlodipine in human plasma. It is suitable for pharmacokinetic study of amlodipine besylate tablets in healthy volunteers.