HPLC-MS/MS法测定大鼠血浆中异绿原酸B浓度及其在药代动力学研究中的应用(英文)
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  • 英文篇名:Rapid and sensitive HPLC-MS/MS method for quantitative determination of isochlorogenic acid B in rat plasma and its application in pharmacokinetic study
  • 作者:刘鑫 ; 张波 ; 梅丹 ; 黄凯
  • 英文作者:Xin Liu;Bo Zhang;Dan Mei;Kai Huang;Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College;State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College;Drug Clinical Trial Institution, Wuxi People' Hospital, Nanjing Medical University;
  • 关键词:异绿原酸B ; LC-ESI-MS/MS ; 血浆药物浓度 ; 药代动力学
  • 英文关键词:Isochlorogenic acid B;;LC-ESI-MS/MS;;Plasma concentration;;Pharmacokinetics
  • 中文刊名:XYGZ
  • 英文刊名:中国药学(英文版)
  • 机构:中国医学科学院北京协和医院药剂科;中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室;南京医科大学附属无锡市人民医院;
  • 出版日期:2019-03-29 18:29
  • 出版单位:Journal of Chinese Pharmaceutical Sciences
  • 年:2019
  • 期:v.28
  • 基金:Chinese Academy of Medical Sciences(Grant No.CAMS-2017-I2M-1-011)
  • 语种:英文;
  • 页:XYGZ201903003
  • 页数:7
  • CN:03
  • ISSN:11-2863/R
  • 分类号:29-35
摘要
建立大鼠血浆中异绿原酸B的LC-MS/MS测定方法,研究大鼠口服异绿原酸B后的血浆药代动力学特征。血浆样品中加入内标白藜芦醇后经甲醇沉淀蛋白。HPLC分离采用Zorbax SB-C_(18)(3.5μm,2.1mm×100mm)柱,流动相为含0.1%甲酸的甲醇–水,流速为0.2mL/min。质谱检测采用电喷雾离子源,负离子选择反应监测(SRM)模式检测m/z515.3→352.9(异绿原酸B)和m/z227.1→143.1(白藜芦醇,内标)。标准曲线在5–2500ng/mL范围内线性良好(r~2=0.9982),日内、日间精密度(RSD)小于12.46%,准确度在±5.80%范围内,血浆样品稳定性好。该方法已成功应用于大鼠血浆异绿原酸B的药代动力学研究。结果表明,在5–20 mg/kg剂量范围内,异绿原酸B在大鼠体内呈非线性的药代动力学特征。
        A sensitive LC-ESI-MS/MS method for determination of isochlorogenic acid B in rat plasma was developed and validated in the present study. Plasma samples were prepared by a simple protein precipitation with methanol containing resveratrol as internal standard(IS). The chromatographic separation was performed on a Zorbax SB-C_(18) column(3.5 μm, 2.1 mm×100 mm, Agilent, USA) at a flow rate of 0.2 mL/min using methanol/water containing 0.1% formic acid(v/v) as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with Electronic Spray Ion by selected reaction monitoring(SRM) of the transitions at m/z 515.3→352.9 for isochlorogenic acid B and m/z 227.1→143.1 for IS, respectively. The calibration curve of the method was linear over the range of 5–2500 ng/mL(r~2 = 0.9982). The intra-and inter-day precisions(R.S.D.%) were less than 12.46%, and the accuracy(R.E.%) was within ±5.80%. Isochlorogenic acid B was sufficiently stable under all relevant analytical conditions. The validated method was successfully applied to the plasma pharmacokinetic studies of isochlorogenic acid B in rats. It was found that isochlorogenic acid B had non-linear pharmacokinetic characteristics in rats within the dosage ranges from 5 to 20 mg/kg.
引文
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