LC-MS／MS法研究氨金黄敏颗粒中对乙酰氨基酚、盐酸金刚烷胺和马来酸氯苯那敏的人体药动学及相对生物利用度  

Pharmacokinetics and bioavailability of paracetamol,amantadine hydrochloride and chlorphenamine maleate in paracetamol,amantadine hydrochloride,artificial cow-bezoar and chlorphenamine maleate granules in Chinese healthy volunteers by LC-MS/MS method

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

机构地区：[1]中国药科大学药物分析室,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：《中国新药杂志》2008年第5期412-417,共6页Chinese Journal of New Drugs

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、盐酸金刚烷胺和马来酸氯苯那敏,并研究健康受试者单剂量口服氨金黄敏颗粒参比和试验制剂后的药动学和相对生物利用度。方法:20名健康男性受试者进行随机双交叉试验,分别单剂量口服2袋氨金黄敏颗粒(每袋含对乙酰氨基酚150mg,盐酸金刚烷胺50mg,人工牛黄10mg,马来酸氯苯那敏2mg)参比制剂和试验制剂。以盐酸克仑特罗为内标,采用ESI正离子选择性反应监测测定对乙酰氨基酚、盐酸金刚烷胺和马来酸氯苯那敏血浆浓度,计算药动学参数及进行上述三成份的生物利用度评价。结果:由AUC0-τ估算,试验制剂中对乙酰氨基酚、盐酸金刚烷胺和马来酸氯苯那敏的相对生物利用度(F)分别为(99.6±19.8)%,(98.9±16.0)%,(87.8±13.5)%。结论:建立的LC-MS/MS测定法准确、灵敏,结果可靠;统计分析表明氨金黄敏颗粒试验制剂和参比制剂中对乙酰氨基酚、盐酸金刚烷胺和马来酸氯苯那敏的吸收、分布、消除速率与程度均无明显差异。Objective： To establish an accurate and sensitive LC-MS/MS method for simultaneous determination of paracetamol, amantadine hydrochloride, cblorpbenamine maleate in plasma and to evaluate their pharmacokinetics and bioavailability in healthy male volunteers after a single oral dose of paracetamol, amantadine hydrochloride, artificial cow-bezoar and chlorphenamine maleate granules. Methods： 20 healthy male volunteers were enrolled in a randomized two-way cross-over design. A single oral dose of 2 bags of test or reference granules （each bag contains 150 mg paracetamol, 50 mg amantadine hydrochloride, 10 mg artificial cow-bezoar, 2 mg chlorphenamine maleate） was given to each volunteer. The concentrations of paracetamol, amantadine bydrochloride and chlorphenamine maleate in plasma were determined by LC-ESI-MS/MS with positive ion MRM detection using clenbuterol hydrochloride as internal standard. The pharmacokinetics and bioavailability of two preparations were compared. Results： The relative bioavailability of the test compared to reference granules were （99.6 ± 19.8）% for paracetamol, （98.9 ± 16.0） % for amantadine hydrochloride, （87.8 ± 13.5 ） % for chlorphenamine maleate. Con elusion： The method was proved to be accurate and sensitive. The results are reliable. The rate and extent of ab sorption, distribution and elimination of paracetamol, amantadine hydrochloride and chlorphenamine maleate be tween test and reference granules were no significance difference.

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

分 类 号：R969.1[医药卫生—药理学]