酚麻氯汀胶囊中氯马斯汀的LC-MS-MS测定方法及在健康人体中的相对生物利用度研究

目的:建立人血浆中氯马斯汀的LC-MS-MS测定法,评价酚麻氯汀胶囊中氯马斯汀在健康人体的相对生物利用度。方法:采用开放、随机、双周期、两制剂、双序列单次给药的交叉试验设计。19例健康志愿者分别口服相当于富马酸氯马斯汀0.67 mg剂量的受试制剂和参比制剂。以硝苯地平为内标,采用甲基叔丁基醚为提取溶剂,用LC-MS-MS法测定血浆中氯马斯汀的质量浓度,经WinNonlin 6.0软件处理血药质量浓度数据后得药动学数据。结果:氯马斯汀的线性范围为5.09~407.20 ng·L-1,定量下限为5.09ng·L-1,绝对回收率为79.7%~80.6%,绝对基质效应为101.0%~103.6%,批内和批间精密度与准确度均符合要求。受试制剂中氯马斯汀的t1/2为(20.67±3.56)h,Cmax为(142.07±65.69)ng·L-1,Tmax为(4.21±1.23)h,AUC0-t为(2 829±1 681)ng·h·L-1;参比制剂中氯马斯汀的的t1/2为(20.83±4.94)h,Cmax为(1 46.55±60.16)ng·L-1,Tmax为(4.13±1.27)h,AUC0-t为(2 839±1 560...

Determination by HPLC-MS-MS method and bioequivalence of clemastine in health volunteers

Objective: To develop an HPLC-MS-MS assay for determination of clemastine in human plasma,and estimate the bioequivalence of clemastine in paracetamol,clemastine fumarate and pseudoephedrine hydrochloride capsule in healthy volunteers.Methods: An open,randomized,two-periods,two-treatment,two-sequence,and crossover clinical trial was performed in 19 healthy male volunteers.They were orally administrated with a single dose of clemastine fumarate 0.67 mg.The plasma concentration of clemastine was determined by...