LC-MS／MS测定健康人体内乌苯美司浓度及其药动学(英文)  

Determination of ubenimex in healthy volunteers by liquid chromatography with tandem mass and its pharmacokinetics

作　　者：孙颖光[1] 张淑慧[1] 赫立恩[1] 马杰[1] 

机构地区：[1]河北省人民医院药学部,河北石家庄050051

出　　处：《中国新药与临床杂志》2009年第8期576-581,共6页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的建立测定人血浆中乌苯美司的液相色谱-串联质谱(LC-MS/MS)方法。方法采用Inertsil ODS-3(50mm×2.1mm,5μm)色谱柱,流动相为甲醇-20mmol·L-1甲酸铵(含0.05%甲酸)(50∶50,V/V),流速:0.3mL·min-1;质谱仪离子源为电喷雾离子源(ESI),正离子模式检测,监测离子为309.55→119.88(乌苯美司)和339.25→280.8(溴莫普林,内标)。结果乌苯美司在2～3000μg·L-1线性关系良好(r=0.9982),定量限为2μg·L-1。主要药动学参数分别为:ρmax(2702±s431)μg·L-1,tmax(0.58±0.26)h,t虔蚝α(0.53±0.17)h,t虔蚝β(1.9±0.5)h,AUC0～t(3744±574)μg·h·L-1,Vc/F(0.0080±0.0020)L,CL(0.0082±0.0012)L·h-1。结论本方法操作简便、准确、灵敏,适用于乌苯美司的人体药动学研究。AIM To develop a sensitive and selective liquid chromatography-tandem mass spectrometric （LC-MS/MS） method for the determination of ubenimex in human plasma. METHODS The analyte was isocratically eluted on a Inertsil ODS-3 column （50 mm × 2.1 mm, 5μm） with methanol-20 mmol·L^-1 ammonium formate （containing 0.05% formate acid） （50 ： 50, V/V） at a flow rate of 0.3 mL·min^-1, and detected with a triple quad LC-MS/MS using ESI with positive ionization. Ions monitored in the selected reaction monitoring （SRM） mode were m/z 309.55→119.88 for ubenimex and m/z 339.25 → 280.8 for brodimoprim （internal standard）. RESULTS The method was sensitive with a lower limit of quantitation （LLOQ） of 2μg·L^-1, with good linearity （r = 0.998 2） over the linear range of 2 - 3 000μg·L^-1. The main pharmacokinetics parameters of ubenimex were as follows： ρmax （2 702± s 431）μg·L^-1, tmax （0.58± 0.26） h, t1/2α （0.53 ± 0.17） h, t1/2β （1.9 ± 0.5） h, AUC0-4 （3 744 ± 574） μg·h·L^-1, Vc/F （0.008 0 ± 0.002 0） L, CL （0.008 2 ± 0.001 2） L·h^-1. CONCLUSION The method was proved to be accurate, sensitive, selective, and convenient and can he applied to study the pharmacokinetics of ubenimex in healthy Chinese volunteers.

关 键 词：乌苯美司 色谱法 高压液相 光谱法 质量 电喷雾电离 药动学 

分 类 号：R961[医药卫生—药理学]