HPLC-MS/MS测定人血浆中青藤碱浓度及芪麝丸在人体内的药代动力学分析

李雪; 李翠; 崔学军; 王拥军; 施杞; 王菊勇

doi:10.13422/j.cnki.syfjx.2017090085

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HPLC-MS/MS测定人血浆中青藤碱浓度及芪麝丸在人体内的药代动力学分析

药物代谢 | 更新时间：2024-01-04

- HPLC-MS/MS测定人血浆中青藤碱浓度及芪麝丸在人体内的药代动力学分析
- Determination of Sinomenine in Human Plasma by HPLC-MS/MS and Pharmacokinetic Analysis of Qishe Pills in Human
- 中国实验方剂学杂志 2017年23卷第9期页码：85-89
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金面上项目（81373622）;国家自然科学基金青年基金项目（81503597）;上海市三年行动计划中医药传承创新平台建设项目（ZY3-CCCX-2-1002）;上海市三年行动计划中医药创新内涵建设项目（ZY3-CCCX-3-2005）
- DOI：10.13422/j.cnki.syfjx.2017090085
  中图分类号： R285.6
- 纸质出版日期：2017
- 稿件说明：
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李雪, 李翠, 崔学军, 等. HPLC-MS/MS测定人血浆中青藤碱浓度及芪麝丸在人体内的药代动力学分析[J]. 中国实验方剂学杂志, 2017,23(9):85-89.

LI Xue, LI Cui, CUI Xue-jun, et al. Determination of Sinomenine in Human Plasma by HPLC-MS/MS and Pharmacokinetic Analysis of Qishe Pills in Human[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(9): 85-89.
李雪, 李翠, 崔学军, 等. HPLC-MS/MS测定人血浆中青藤碱浓度及芪麝丸在人体内的药代动力学分析[J]. 中国实验方剂学杂志, 2017,23(9):85-89. DOI： 10.13422/j.cnki.syfjx.2017090085.

LI Xue, LI Cui, CUI Xue-jun, et al. Determination of Sinomenine in Human Plasma by HPLC-MS/MS and Pharmacokinetic Analysis of Qishe Pills in Human[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(9): 85-89. DOI： 10.13422/j.cnki.syfjx.2017090085.

摘要

目的：建立简便、灵敏的检测人血浆中青藤碱浓度的高效液相色谱-三重四极杆质谱联用技术（HPLC-MS/MS），研究健康受试者口服芪麝丸后青藤碱的体内药代动力学特征。方法：血浆样品中加入内标（普萘洛尔），加甲醇沉淀蛋白后分离上清液进行检测，流动相甲醇-水（含0.1%甲酸+5 mmol·L-1甲酸铵）进行梯度洗脱。质谱采用电喷雾电离源（ESI），选择反应离子监测模式，用于定量分析的青藤碱和普萘洛尔离子对的m/z分别为（330.2~152.2和260.2~183.1）。利用WinNonlin 6.3软件计算人口服芪麝丸后青藤碱的药动学参数。结果：人血浆中青藤碱线性范围5~1 000 μg·L-1，定量下限5.0 μg·L-1，批内和批间准确度偏差均在±10.0%以内，RSD均<15.0%，青藤碱的回收率103.3%，无明显基质效应，稳定性良好。人口服芪麝丸后血浆中青藤碱的主要药动学参数达峰时间（Tmax），药峰浓度（Cmax），药时曲线下面积（AUC0-48 h），半衰期（t1/2）分别为（2.5±0.8）h，（477.9±60.1）μg·L-1，（4 808.8±791.7）h·μg·L-1，（7.5±1.3）h。结论：建立的方法简便、快速、灵敏、可靠，可用于研究人口服芪麝丸后青藤碱的药代动力学特征，为该制剂的致敏机制和药代-药效研究提供一定的方法学基础和数据。

Abstract

Objective: To develop a simple

rapid and accurate HPLC-MS/MS for the determination of sinomenine in human plasma and study on pharmacokinetics of sinomenine after oral administration of Qishe pills. Method: Human plasma samples were prepared by protein precipitation method with methanol as solvent.The separation of sinomenine and propranolol (the internal standard

IS) was performed on a ZORBAX SB-C18 column with mobile phase of methanol-water (containing 0.1% formic acid and 5 mmol·L-1 ammonium formate) for gradient elution.Electrospray ionization (ESI) mass spectrometry was operated in the positive ion mode with selected reaction monitoring (SRM) of the transitions at m/z 330.2-152.2 for sinomenine and m/z 260.2-183.1 for IS.Pharmacokinetic parameters were calculated by WinNonlin 6.3 software. Result: The linear range of sinomenine in human plasma was 5-1 000 μg·L-1 with the lower limit of quantitation (LLOQ) of 5.0 μg·L-1

the relative standard deviations of intra-batch and inter-batch precision were below 15.0%

while the deviations of assay accuracy were within ±10.0%.The extraction recovery of sinomenine was 103.3% and no obvious matrix effect was observed.The main pharmacokinetic parameters of sinomenine (Tmax

Cmax

AUC0-48 h and t1/2) after oral administration of Qishe pills were (2.5±0.8) h

(477.9±60.1) μg·L-1

(4 808.8±791.7) h·μg·L-1 and (7.5±1.3) h

respectively. Conclusion: The validated method is successfully applied to pharmacokinetics of sinomenine in human after oral administration of Qishe pills

which can provide a methodological basis and data for the future clinical studies of this preparation.

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