LC-MS／MS测定盐酸他利克索与美多芭联合用药的人体药动学  

Pharmacokinetic Study of Talipexole Hydrochloride in Combination With Madopar in Human Plasma by LC-MS/MS

作　　者：张婷婷[1] 徐晓峰[1] 杭太俊[1] 宋敏[1] 文爱东[2] 

机构地区：[1]中国药科大学药学院药物分析教研室,南京210009 [2]第四军医大学西京医院国家药品临床研究基地,西安710032

出　　处：《中国药学杂志》2008年第5期365-369,共5页Chinese Pharmaceutical Journal

摘　　要：目的建立液相色谱-串联质谱法研究盐酸他利克索与关多芭联合用药在健康志愿者体内的药动学行为。方法以盐酸克仑特罗为内标,血浆样品经乙酸乙酯提取,Lichrospher C_6H_6柱分离后电喷雾正离子化选择性反应检测。12名健康志愿者(男女各半)按随机双交叉试验设计,研究单剂量口服盐酸他利克索片(0.4 mg)及与美多芭片(0.25 g)联合用药后的药动学。结果盐酸他利克索在0.10～10.0μg·L^(-1)内呈现良好线性,方法回收率为80.8%～86.2%。日内、日间精密度的RSD分别为0.5%～4.8%和2.4%～8.6%。两种服药方式后盐酸他利克索的主要药动学参数ρ_(max),t_(max),t_(1/2),MRT,AUC_(0-36),AUC_(0-∞),CL/F和V_d/F分别为(0.96±0.12)和(0.89±0.16)μg·L^(-1),(1.4±0.9)和(1.4±0.9)h,(11.37±1.99)和(11.61±1.80)h,(15.90±2.95)和(16.35±2.60)h,(9.66±1.33)和(9.36±1.58)μg·h·L^(-1),(11.07±1.72)和(10.82±1.98)μg·h·L^(-1),(37.9±7.50)和(40.5±10.0)L·h^(-1),(650±186)和(601±167)L。经单因素方差分析及独立样本t检验分析单剂量口服盐酸他利克索片及与美多芭片联合用药后的主要药动学参数均无显著性差异。结论建立的LC-MS/MS测定法准确、灵敏,专属。美多芭对盐酸他利克索的药动学行为没有明显影响。OBJECTIVE To develop a sensitive LC-MS/MS method for pharmacokinetic study of talipexole hydrochloride in combination with madopar in human plasma. METHODS Clenbuterol hydrochloride was used as internal standard （IS）. Liquid-liquid extraction with ethyl acetate was used for sample preparation. Chromatographic separation was can＇ied on a Lichrospher C6 H6 column with MS/MS detection by using positive electrospray ionization and selective reaction monitoring. A single oral dose of 0. 4 mg talipexole hydrochloride tablets or talipexole in combination with 0. 25 g madopar were given to 12 healthy volunteers in this open-label, randomized, crossover study. RESULTS The calibration curve was linear within the range of 0. 10 - 10. 0 μg·L^-1, the method recovery was 80. 8% - 86. 2% , RSDs of intra-day and inter-day were 0. 5% - 4. 8% and 2. 4% - 8. 6%, respectively, ρmax,tmax,t1/2 , MRT, AUC0-36, AUC0-∞ , CL/F and Vd/F of talipexole hydrochloride after a single oral dose of 0. 4 mg talipexole hydrochloride tablets and talipexole in combination with 0. 25 g madopar were （0. 96±0. 12） and （0. 89 ±0. 16） μg·L^-1, （1.4 ±0. 9） and （1.4 ±0. 9） h, （11.37±1.99） and （11.61 ±1.80） h, （15.90±2.95） and （16.35±2.60） h, （9.66±1.33） and （9.36±1.58） μg·h·L^-1, （11.07±1.72） and （10.82±1.98） μg·h·L^-1, （37.9±7.50） and （40.5±10.0） L·h^-1, （650±186） and （601±167） L, respectively. There were no significant differences between two administrations assessed by One-way ANOVA and independent-samples t test. CONCLUSION The LC-MS/MS method was sensitive and selective with no endogenous interferences. The plasma pharmacokinetics of talipexole hydrochloride was not affected by the co-administration of madopar.

关 键 词：盐酸他利克索 美多芭 LC-MS/MS 药动学 

分 类 号：R969.1[医药卫生—药理学] R917[医药卫生—药学]