【摘要】 目的：建立人血浆中米拉贝隆浓度的LC-MS/MS测定方法，并评价其在中国健康受试者体内的药动学特征。方法：在冰浴条件下，经蛋白沉淀法进行血浆样品前处理，采用ACE Excel 3 AQ（2.1 mm×100 mm）色谱柱，流动相为5.00 mmol·L-1醋酸铵水溶液（含0.1%甲酸）及5.00 mmol·L^-1醋酸铵-90%乙腈水溶液（含0.1%甲酸），流速为0.400 mL·min^-1；多反应监测正离子模式，米拉贝隆和米拉贝隆-d5的检测反应离子对分别为m/z 397.2→260.0和m/z402.2→260.0。入选20名中国健康受试者，空腹单次口服米拉贝隆缓释片50 mg，于不同采血时间点将全血采集至含氟化钠的肝素钠采血管中，分离得到血浆样品进行LC-MS/MS检测。结果：血浆中米拉贝隆的线性范围为0.160～85.0 ng·mL^-1, 20名受试者单次口服米拉贝隆缓释片50 mg后的药代动力学参数：AUC0-t为（304±136） h·ng·mL^-1,AUC0-∞为（342±153）h·ng·mL^-1,t_1/2为（34.1±6.58）h,tmax为（4.16±1.10）h,Cmax为（35.3±21.7）ng·mL^-1。结论：本研究建立了人血浆中米拉贝隆的LC-MS/MS测定方法，该方法快速、灵敏、准确、专属性强，可应用于该药的中国健康受试者人体药代动力学研究。更多还原

【Abstract】 Objective: To develope an LC-MS/MS method to determine the concentrations of mirabegron in human plasma and to evaluate its pharmacokinetic characteristics in healthy Chinese subjects. Methods: The plasma samples were pretreated by protein precipitation in ice bath, injected to an ACE Excel 3 AQ（2.1 mm ×100 mm） column and eluted with gradient mobile phase of 5.00 mmol·L^-1ammonium acetate aqueous solution（containing 0.1% formic acid） and 5.00 mmol·L^-1ammonium acetate-90% acetonitrile aqueous solution（containing 0.1% formic acid） at a flow rate of 0.400 mL·min^-1. The positive ion mode was monitored in multiple reactions, and the detected reaction ion pairs were m/z 397.2 → 260.0 and m/z 402.2 → 260.0 for mirabegron and mirabegron-d5, respectively. Twenty healthy Chinese subjects were enrolled and each received a single oral dose of 50 mg of mirabegron sustained-release tablets on an empty stomach. Whole blood samples were collected from 0 h to 96 h in sodium heparin collection tubes containing sodium fluoride for plasma separation and LC-MS/MS detection. Results: The linear range of mirabegron in human plasma was 0.160 to 85.0 ng·mL^-1.For mirabegron in the tested Chinese subjects, AUC0-twas（304 ± 136） h·ng·mL^-1; AUC0-∞was（342 ± 153） h·ng·mL^-1; t_1/2was（34.1 ± 6.58） h; tmaxwas（4.16 ± 1.10） h; C_max was（35.3 ± 21.7） ng·mL^-1. Conclusions: A rapid,sensitive, accurate and specific LC-MS/MS method for the determination of mirabegron in human plasma was developed, which could be applied to the pharmacokinetic study of this drug in Chinese healthy subjects.更多还原