药学学报, 2013, 48(6): 917-924
引用本文:
李 涛, 王怡薇, 王彦礼, 梁日欣, 张 东, 张会会, 陈 立, 周钟鸣, 杨伟鹏. 黄芩汤血浆中多成分LC-MS法测定及其药代动力学特征研究[J]. 药学学报, 2013, 48(6): 917-924.
LI Tao, Wang Yi-Wei, Wang Yan-Li, Liang Ri-Xin, Zhang Dong, Zhang Hui-Hui, Chen Li, Zhou Zhong-Ming, Yang Wei-Peng. LC-MS quantification and pharmacokinetics of the multi-constituents of Huangqin Tang in rat plasma after different single oral doses[J]. Acta Pharmaceutica Sinica, 2013, 48(6): 917-924.

黄芩汤血浆中多成分LC-MS法测定及其药代动力学特征研究
李  涛, 王怡薇, 王彦礼, 梁日欣, 张  东, 张会会, 陈  立, 周钟鸣, 杨伟鹏*
(中国中医科学院中药研究所, 北京 100700)
摘要:

LC-MS法测定大鼠灌胃黄芩汤后血浆中黄酮类和萜类成分, 并研究不同剂量黄芩汤在大鼠体内的药代动力学特征。血浆样品经盐酸和抗坏血酸处理, 乙腈沉淀蛋白, LC-MS测定, WinNonlin软件计算药代动力学参数。方法经特异性、线性范围、准确度、精密度、稳定性等确证适合血浆中8个成分的测定; 时曲线黄芩苷、汉黄芩苷、黄芩素、汉黄芩素、千层纸素A和甘草酸有双峰现象; 黄芩汤1040 g·kg−1给药, 8个成分的体内暴露量与剂量呈依赖关系; 血浆中同一类成分, 黄芩苷和汉黄芩苷, 黄芩素和汉黄芩素、千层纸素A的体内过程类似。本方法简单、专属, 能用于血浆中芍药苷、黄芩苷、汉黄芩苷、黄芩素、汉黄芩素、千层纸素A、甘草酸和甘草次酸的同时测定, 各成分在体内具有良好的药代动力学特征。

关键词:   
LC-MS quantification and pharmacokinetics of the multi-constituents of Huangqin Tang in rat plasma after different single oral doses
Abstract:

The current study aims to investigate the pharmacokinetic properties of Huangqin Tang on different oral doses.  An LC-MS method for simultaneous determination of flavonoids and terpenoids in rat plasma was developed and validated.  Plasma samples were treated with hydrochloric acid (containing 1% ascorbic acid), precipitated with acetonitrile, separated on a Zorbax SB-C18 column, detected by single quadruple mass spectrometry with an electrospray ionization interface, and quantified using selected ion monitoring mode.  All pharmacokinetic parameters were processed by non-compartmental analysis using WinNonlin software.  The results of specificity, linearity, intra-day and inter-day precisions, accuracy, and stability for LC-MS assay were suitable for the quantification of paeoniflorin, baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid in rat plasma.  The concentration–time profiles of baicalin, wogonoside, baicalein, wogonin, oroxylin A and glycyrrhizic acid showed double-peak phenomenon after Huangqin Tang was orally administered at 40 g?kg−1 dose; all eight constituents in rat plasma showed good dose-exposure relationship within the dosage of 10-40 g?kg−1; although plasma concentrations were different, the flavonoids with the same backbone showed the similar fate in the body with the corresponding dosage.  In conclusion, the LC-MS assay was successfully applied for the pharmacokinetic study of multi-constituents of Huangqin Tang with different doses.  Additionally, these constituents demonstrated good pharmacokinetic properties in the body.

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