快速高分辨液相色谱-质谱联用技术分析2型糖尿病大鼠口服四君子汤的药代动力学

doi:10.19894/j.issn.1000-0518.200362

摘要/Abstract

摘要： 研究四君子汤在2型糖尿病大鼠体内的药代动力学。将四君子汤水提物以18 g/kg给正常大鼠和2型糖尿病大鼠灌胃,分别在不同时间点取尿液和粪便,检测其成分及代谢产物的含量;比较正常大鼠和2型糖尿病大鼠的药代动力学参数。采用快速高分辨液相色谱-质谱联用技术对人参皂苷Rc、甘草甜素及其脱糖代谢物进行表征。结果表明,四君子汤中人参皂苷Rc和甘草甜素在2型糖尿病大鼠体内的累计排泄率均高于正常大鼠,大部分人参皂苷通过尿液排出体外、粪便代谢为稀有人参皂苷;大部分甘草甜素在尿液和粪便中转化为甘草次酸,2型糖尿病大鼠与正常大鼠人参皂苷Rc和甘草甜素的药代动力学参数存在明显差异。初步总结了四君子汤在体内的药代动力学机制和代谢途径。本分析方法具有高度自动化,灵敏性和准确性,这将有助于四君子汤的临床研究的不断发展。

关键词: 四君子汤, 药物动力学, 2型糖尿病, 快速分辨液相色谱-质谱联用仪

Abstract: To study the pharmacokinetics of Sijunzi Decoction in type 2 diabetes rats. The water extract of Sijunzi Decoction was given to normal rats and type 2 diabetic rats by gavage at 18 g/kg. The urine and feces were collected at different time points, and the contents of its components and metabolites were detected. The pharmacokinetic parameters of normal rats and type 2 diabetic rats were compared by using rapid resolution liquid chromatography/tandem mass spectrometry (RRLC/MS). Ginsenoside Rc, glycyrrhiza and their metabolites were characterized by fast high resolution liquid chromatography-mass spectrometry. In Sijunzi Decoction, the cumulative excretion rate of ginsenoside Rc and glycyrrhizin in type 2 diabetic rats is higher than that in normal rats. Most ginsenosides are excreted in urine and metabolized into rare ginsenosides in feces. Most of glycyrrhizin is converted to glycyrrhetinic acid in urine and feces. There are significant differences in pharmacokinetic parameters of ginsenoside Rc and glycyrrhizin between type 2 diabetic rats and normal rats. The pharmacokinetic mechanism and metabolic pathway of Sijunzi Decoction in vivo were summarized.

Key words: Sijunzi Decoration, Pharmacokinetics, Type 2 diabetes, Rapid resolution liquid chromatography/tandem mass spectrometry

中图分类号:

O629

高松红, 杨迪, 李忠起, 郑飞, JEON You-Jin, 戴雨霖. 快速高分辨液相色谱-质谱联用技术分析2型糖尿病大鼠口服四君子汤的药代动力学[J]. 应用化学, 2021, 38(3): 315-322.

GAO Song-Hong, YANG Di, LI Zhong-Qi, ZHENG Fei, JEON You-Jin, DAI Yu-Lin. Rapid Resolution Liquid Chromatography with Tandem Mass Spectrometry on Pharmacokinetics of Type 2 Diabetic Rats with Oral Administration of Sijunzitang Decoration[J]. Chinese Journal of Applied Chemistry, 2021, 38(3): 315-322.

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