LC-MS/MS法测定人血浆中米拉贝隆及其中国健康人体药动学研究  

An LC-MS/MS Method of Human Plasma Mirabegron Determination for Its Pharmacokinetic Study

作　　者：陈敏 范宇轩 程旻露 刘海俊 丁黎[2] CHEN Min;FAN Yuxuan;CHENG Minlu;LIU Haijun;DING Li(Zhuhai Tongyuan Pharmaceutical Co,Zhuhai,Guangdong 519041,China;Department of Pharmaceutical Analysis,China Pharmaceutical University,Nanjing 211100,China;Nanjing Clinical Tech.Laboratories Inc.,Nanjing 211100,China)

机构地区：[1]珠海同源药业有限公司,广东珠海519041 [2]中国药科大学药物分析研究室,南京211100 [3]南京科利泰医药科技有限公司,南京211100

出　　处：《药学与临床研究》2022年第6期497-500,共4页Pharmaceutical and Clinical Research

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),t1/2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。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^(-1)ammonium acetate aqueous solution(containing 0.1% formic acid) and 5.00 mmol·L^(-1)ammonium 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);t1/2was(34.1 ± 6.58) h;tmaxwas(4.16 ± 1.10) h;Cmaxwas(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.

关 键 词：LC-MS/MS 米拉贝隆 药代动力学 中国健康受试者 膀胱过度活动症 

分 类 号：R969[医药卫生—药理学]