代谢产物鉴定及汉黄芩素与汉黄芩素-7-O-葡萄糖醛酸苷的同时测定: 小鼠肝脏的分布研究

doi:10.5246/jcps.2011.03.035

代谢产物鉴定及汉黄芩素与汉黄芩素-7-O-葡萄糖醛酸苷的同时测定: 小鼠肝脏的分布研究

柳文媛, 杨晓静, 冯锋^*, 徐晓珍

1. 中国药科大学药物分析教研室, 江苏南京 210009
2. 中国药科大学药物质量与安全预警教育部重点实验室, 江苏南京 210009
3. 中国药科大学天然药物化学教研室, 江苏南京 210009

收稿日期:2011-01-04 修回日期:2011-03-09 出版日期:2011-05-06 发布日期:2011-05-06
通讯作者: 冯锋*

Metabolite identification and the development of a simultaneous quantification method for wogonin and wogonin-7-O-glucuronide: application to a distribution study in mice liver

Wen-Yuan Liu, Xiao-Jing Yang, Feng Feng^*, Xiao-Zhen Xu

1. Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China
2. Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China
3. Department of Phytochemistry, China Pharmaceutical University, Nanjing 210009, China

Received:2011-01-04 Revised:2011-03-09 Online:2011-05-06 Published:2011-05-06
Contact: Feng Feng*

摘要/Abstract

摘要：

汉黄芩素具有体内外抗肿瘤活性及良好的安全性。本文采用高效液相色谱串联质谱法研究了小鼠静脉注射汉黄芩素后肝脏中的代谢产物, 鉴定了五个主要的代谢产物。建立了小鼠肝脏中汉黄芩素及其代谢产物汉黄芩素-7-O-葡萄糖醛酸苷的同时测定方法。肝匀浆经醋酸乙酯提取, 在C18色谱柱上, 采用甲醇-10 mM 醋酸铵 (80:20, v/v)为流动相, 质谱检测采用负离子选择反应监测模式。肝组织中汉黄芩素与汉黄芩素-7-O-葡萄糖醛酸苷在0.2-40 μg/g范围内呈良好线性关系, 方法学评价表明本法适用于动物静脉注射汉黄芩素后体内的组织分布研究。

关键词: 汉黄芩素, 汉黄芩素-7-O-葡萄糖醛酸苷, 代谢产物, 液相色谱-质谱联用

Abstract:

Wogonin possesses potent inhibitory activities against cancer cell growth in vitro and in vivo and has attractive safety profiles. A highly sensitive liquid chromatography coupled with tandem mass spectrometry method was developed for the identification of major metabolites in mice liver after intravenous administration of wogonin. Five metabolites were identified and biotransformation pathways were elucidated as well. Furthermore, a method was developed and validated for the simultaneous quantitatively determination of wogonin and wogonin-7-O-glucuronide in mice liver. After liquid-liquid extraction by ethyl acetate, the analytes were separated on a C18 column with a mobile phase of methanol-10 mM ammonium acetate water (80:20, v/v). The detection was operated with negative selected reaction monitoring mode using electrospray ionization technique. The linear response range was 0.2-40 μg/g for both wogonin and wogonin-7-O-glucuronide in mice liver. The developed quantification method was suitable for distribution study after intravenous infusion of wogonin injection in animals.

Key words: Wogonin, Wogonin-7-O-glucuronide, Metabolite identification, Liquid chromatography-tandem mass spectrometry

中图分类号:

R969.1

Supporting:

Foundation item: China National Key Hi-Tech Innovation Project for the R&D of Novel Drugs (Grant No. 2009zx09102-032).
^*Corresponding author. Tel.: 86-25-83271517

柳文媛, 杨晓静, 冯锋^*, 徐晓珍. 代谢产物鉴定及汉黄芩素与汉黄芩素-7-O-葡萄糖醛酸苷的同时测定: 小鼠肝脏的分布研究[J]. , DOI: 10.5246/jcps.2011.03.035.

Wen-Yuan Liu, Xiao-Jing Yang, Feng Feng^*, Xiao-Zhen Xu. Metabolite identification and the development of a simultaneous quantification method for wogonin and wogonin-7-O-glucuronide: application to a distribution study in mice liver[J]. , DOI: 10.5246/jcps.2011.03.035.

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