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

doi:10.5246/jcps.2019.03.016

中国药学(英文版) ›› 2019, Vol. 28 ›› Issue (3): 167-173.DOI: 10.5246/jcps.2019.03.016

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

刘鑫^1,2, 张波¹, 梅丹¹, 黄凯^3*

1. 中国医学科学院北京协和医院药剂科, 北京 100730
2. 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, 北京 100050
3. 南京医科大学附属无锡市人民医院, 江苏无锡 214013

收稿日期:2018-12-30 修回日期:2019-01-05 出版日期:2019-03-30 发布日期:2019-02-17
通讯作者: Tel.: +86-010-85350347, E-mail: hk19820627@sina.com
基金资助:
Chinese Academy of Medical Sciences (Grant No. CAMS-2017-I2M-1-011).

Rapid and sensitive HPLC-MS/MS method for quantitative determination of isochlorogenic acid B in rat plasma and its application in pharmacokinetic study

Xin Liu^1,2, Bo Zhang¹, Dan Mei¹, Kai Huang^3*

1. Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
2. 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, Beijing 100050, China
3. Drug Clinical Trial Institution, Wuxi People’ Hospital, Nanjing Medical University, Wuxi 214023, China

Received:2018-12-30 Revised:2019-01-05 Online:2019-03-30 Published:2019-02-17
Contact: Tel.: +86-010-85350347, E-mail: hk19820627@sina.com
Supported by:
Chinese Academy of Medical Sciences (Grant No. CAMS-2017-I2M-1-011).

摘要/Abstract

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-C₁₈(3.5 μm, 2.1 mm×100 mm)柱,流动相为含0.1%甲酸的甲醇–水,流速为0.2 mL/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5–2500 ng/mL范围内线性良好(r²= 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。

关键词: 异绿原酸B, LC-ESI-MS/MS, 血浆药物浓度, 药代动力学

Abstract:

Asensitive 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-C₁₈column (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 detectionwas 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 (r²= 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.

Key words: Isochlorogenic acid B, LC-ESI-MS/MS, Plasma concentration, Pharmacokinetics

中图分类号:

R969.1

Supporting:

刘鑫, 张波, 梅丹, 黄凯. 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[J]. 中国药学(英文版), 2019, 28(3): 167-173.

Xin Liu, Bo Zhang, Dan Mei, Kai Huang. Rapid and sensitive HPLC-MS/MS method for quantitative determination of isochlorogenic acid B in rat plasma and its application in pharmacokinetic study[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(3): 167-173.

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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

Rapid and sensitive HPLC-MS/MS method for quantitative determination of isochlorogenic acid B in rat plasma and its application in pharmacokinetic study

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