LC-MS／MS法研究氨酚烷胺胶囊的人体药动学及相对生物利用度  

LC-MS/MS determination of pharmacokinetics and bioavailability of compound paracetamol and amantadine capsules in Chinese healthy volunteers

作　　者：狄斌[1] 徐晓峰[1] 陈珺[1] 杭太俊[1] 宋敏[1] 文爱东[2] 杨林[2] 

机构地区：[1]中国药科大学药物分析教研室,南京210009 [2]中国人民解放军第四军医大学临床药理研究所,西安710032

出　　处：《药物分析杂志》2008年第6期877-883,共7页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立准确、灵敏的液相色谱-串联质谱法(LC—MS/MS)同时测定人血浆中的对乙酰氨基酚、盐酸会刚烷胺、咖啡因和马来酸氯苯那敏浓度,并研究健康受试者单剂量口服氨酚烷胺胶囊参比制剂和试验制剂后的药动学和相对生物利用度。方法:24名健康男性受试者进行随机双交叉试验,随机单剂量口服1粒氨酚烷胺胶囊(每粒含对乙酰氨基酚250 mg、盐酸金刚烷胺100 mg、咖啡因15 mg 和马来酸氯苯那敏2 mg)参比制剂和试验制剂后采集血样,以盐酸克仑特罗为内标,采用 ESI 正离子选择性反应监测同时测定对乙酰氨基酚、盐酸金刚烷胺、咖啡因和马来酸氯苯那敏血浆浓度,计算药动学参数及进行生物等效性评价。结果:由 AUC_(0-r)估算,试验制剂中对乙酰氨基酚、盐酸金刚烷胺、咖啡因和马来酸氯苯那敏的相对生物利用度(F)分别为(99.2±21.4)%,(102.8±38.5)%,(112.0±53.1)%,(102.4±43.1)%。结论:建立的 LC—MS/MS 测定法准确、灵敏,结果可靠;统计分析表明氨酚烷胺胶囊试验制剂和参比制剂生物等效。Objective：To establish an accurate and sensitive LC -MS/MS method for the simultaneous determination of paracetamol, amantadine hydrochloride, caffeine, chlorphenamine maleate in human plasma and to evaluate the pharmacokinetics and bioavailability in healthy male volunteers after a single oral dose of compound paracetamol and amantadine capsules. Method：24 healthy male volunteers were divided into a two- way crossover design. A single oral dose of a compound paracetamol and amantadine test or reference capsule （ each containing paracetamol 250 mg,amantadine hydrochloride 100 mg,caffeine 15 mg and chlorphenamine maleate 2 mg） was given to each volunteer according to an open randomized crossover study. The concentrations of paracetamol, amantadine hydrochloride, caffeine and chlorphenamine maleate in plasma were determined by LC - ESI - MS/MS method with positive ion SRM detection using clenbuterol hydrochloride as internal standard. The pharmacokinetics and bioavailabili- ty were compared. Results：The relative bioavailability of the test compared to reference capsules were paracetamol （99.2± 21.4 ） %, amantadine hydrochloride （ 102.8± 38.5 ） %, caffeine （ 112.0 ± 53.1 ） %, chlorphenamine maleate （102.4 ±43.1 ）%. Conclusions：The method proved to be accurate and sensitive. The results are reliable. The compound paracetamol and amantadine capsule was bioequivalent to equivalent dose of reference capsules.

关 键 词：对乙酰氨基酚 盐酸金刚烷胺 咖啡因 马来酸氯苯那敏 药动学 生物利用度 液相色谱-串联质谱 电喷雾离子化 

分 类 号：R917[医药卫生—药物分析学]