Li Tao, Wang Yi-Wei, Wang Yan-Li, Liang Ri-Xin, Zhang Dong, Zhang Hui-Hui, Chen Li, Zhou Zhong-Ming, Yang Wei-Peng
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Yao Xue Xue Bao. 2013 Jun;48(6):917-24.
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 x kg(-1) dose; all eight constituents in rat plasma showed good dose-exposure relationship within the dosage of 10-40 g x 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.
本研究旨在考察不同口服剂量下黄芩汤的药代动力学特性。建立并验证了一种用于同时测定大鼠血浆中黄酮类和萜类化合物的液相色谱-质谱（LC-MS）方法。血浆样品用盐酸（含1%抗坏血酸）处理，用乙腈沉淀，在Zorbax SB-C18柱上分离，采用电喷雾电离接口的单四极杆质谱检测，并用选择离子监测模式进行定量。所有药代动力学参数均使用WinNonlin软件通过非房室分析进行处理。LC-MS测定的特异性、线性、日内和日间精密度、准确度及稳定性结果适用于大鼠血浆中芍药苷、黄芩苷、汉黄芩苷、黄芩素、汉黄芩素、木犀草素、甘草酸和甘草次酸的定量分析。黄芩汤按40 g·kg⁻¹剂量口服给药后，黄芩苷、汉黄芩苷、黄芩素、汉黄芩素、木犀草素和甘草酸的浓度-时间曲线呈现双峰现象；在10 - 40 g·kg⁻¹剂量范围内，大鼠血浆中所有八种成分均呈现良好的剂量-暴露关系；尽管血浆浓度不同，但具有相同骨架的黄酮类化合物在体内随相应剂量呈现相似的转归。总之，LC-MS测定法成功应用于不同剂量黄芩汤多成分的药代动力学研究。此外，这些成分在体内表现出良好的药代动力学特性。
