文章摘要
丁黎,范宇轩,程旻露,刘海俊,陈敏.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[J].药学与临床研究,2022,30(6):497~500
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
投稿时间:2022-07-14  修订日期:2022-12-18
DOI:
中文关键词: 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
英文关键词: LC-MS/MS  Mirabegron  Pharmacokinetics  Chinese healthy subjects  Overactive bladder
基金项目:
作者单位邮编
丁黎 中国药科大学
南京科利泰医药科技有限公司 
211100
范宇轩 中国药科大学药物分析研究室 
程旻露 南京科利泰医药科技有限公司 
刘海俊 南京科利泰医药科技有限公司 
陈敏 珠海同源药业有限公司 
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中文摘要:
      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/z 402.2→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。
英文摘要:
      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-t was (304 ± 136) h·ng·mL-1; AUC0-∞ was (342 ± 153) h·ng·mL-1; t1/2 was (34.1 ± 6.58) h; tmax was (4.16 ± 1.10) h; Cmax 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.
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