代谢分析

桂枝茯苓胶囊在原发性痛经模型大鼠血浆、胆汁、尿液和粪便中的代谢产物研究*

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  • 1.南京中医药大学 江苏省中药资源产业化过程协同创新中心/江苏省方剂高技术研究重点实验室,南京 210023;
    2.南京中医药大学 中药资源产业化与方剂创新药物国家地方联合工程研究中心,南京 210023;
    3.江苏康缘药业股份有限公司,连云港 222001
第一作者 Tel:15951872132;E-mail:zhaoql0508@163.com
** Tel: (025)85811916;E-mail:qiandwnj@126.com

收稿日期: 2020-01-12

  网络出版日期: 2024-05-31

基金资助

* 桂枝茯苓胶囊标准化建设(ZYBZH-C-JS-28)

Analysis of metabolites in primary dysmenorrhea rats plasma, bile,urine and feces after administration of Guizhi Fuling capsules *

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  • 1. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/Jiangsu Key Laboratory for High Technology Research of TCM Formulae,Nanjing University of Chinese Medicine,Nanjing 210023,China;
    2. National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine,Nanjing 210023,China;
    3. Kanion Pharmaceutical Co.,Ltd.,Lianyungang 222001,China

Received date: 2020-01-12

  Online published: 2024-05-31

摘要

目的:研究桂枝茯苓胶囊在原发性痛经模型大鼠体内的代谢产物。方法:基于超高效液相色谱 - 线性离子阱 - 静电轨道阱串联质谱联用(UHPLC-LTQ-Orbitrap-MS)方法,采用 Waters ACQUITY UPLC BEH C18 色谱柱(100 mm×2.1 mm,1.7 μm),以乙腈 -0.1% 甲酸水为流动相,梯度洗脱,流速 0.4 mL·min -1 ,质谱采用电喷雾(ESI)离子源,以正负离子模式采集多级质谱碎片信息,对大鼠灌服桂枝茯苓胶囊混悬液后的血浆、胆汁、尿液和粪便进行分析,利用质量亏损过滤(MDF)技术进行代谢产物鉴定分析。结果:共鉴定出8 个原形及 50 个代谢产物,在体内主要发生Ⅰ相代谢反应(脱羧、水解、脱羟基和脱水等)及Ⅱ相代谢反应(甲基化、乙酰化、硫酸化及葡萄糖醛酸化等)。结论:采用 LC-MS 方法鉴定了原发性痛经模型大鼠体内桂枝茯苓胶囊代谢产物,为该复方制剂的药物代谢动力学研究提供依据。

本文引用格式

赵秋龙, 卞晓坤, 钱大玮, 宿树兰, 郭盛, 王团结, 段金廒 . 桂枝茯苓胶囊在原发性痛经模型大鼠血浆、胆汁、尿液和粪便中的代谢产物研究*[J]. 药物分析杂志, 2021 , 41(1) : 51 -63 . DOI: 10.16155/j.0254-1793.2021.01.06

Abstract

Objective: To determine the metabolites in primary dysmenorrhea rats after administration of Guizhi Fuling capsules. Methods: The ultra-high performance liquid chromatography-LTQ Orbitrap mass spectrometric (UHPLC-LTQ-Orbitrap-MS) and mass defect filter techniques with electrospray ion (ESI) source were applied to collect multi-level mass spectrometry fragment information in both positive and negative ion modes. The separation was performed on a Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm,1.7 μm) with mobile phase of acetonitrile-water (containing 0.1% formic acid) by gradient elution at a flow rate of 0.4 mL·min -1 . After the administration of Guizhi Fuling capsules,the plasma,bile,urine and feces in rats were analyzed,and the metabolites were identified by mass loss filtration (MDF). Results: 8 prototypes and 50 metabolites were determined. The in vivo main metabolic reactions were phase Ⅰ reaction (decarboxylation, hydrolysis,dehydroxylation and dehydration) and phase Ⅱ reaction (methylation,acetylation,sulfonation and glucuronidation). Conclusion: LC-MS isused to identify metabolites of Guizhi Fuling capsules in rats with primary dysmenorrhea,and this study provids a basis for pharmacokinetic studies of the compound preparation of traditional Chinese medicine.

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