Analysis of in Vivo and in Vitro Metabolites of Coptisine in Rats by HPLC-MS/MS
10.13422/j.cnki.syfjx.20200346
- VernacularTitle:HPLC-MS/MS分析黄连碱在大鼠体内外的代谢产物
- Author:
Hong-ying CHEN
1
;
Yun-fang HUANG
1
;
Qi-hua LIU
2
;
Wei ZHENG
1
;
Zhi-hui LI
1
;
Jian-hua CHEN
1
;
Jing QI
1
;
Ting ZHANG
1
;
Gui-jie WEI
1
;
Peng-kai MA
1
;
Yu-jie ZHANG
1
Author Information
1. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
2. Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
- Publication Type:Research Article
- Keywords:
coptisine;
metabolites;
in vivo and in vitro metabolism;
glucuronide conjugation;
liver microsomes;
intestinal flora;
metabolic pathways
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2020;26(9):113-119
- CountryChina
- Language:Chinese
-
Abstract:
Objective::To investigate in vivo and in vitro metabolites of coptisine and their metabolic pathways. Method::SD rats were given coptisine by single gavage (dose of 25 mg·kg-1). Urine and feces from 0 h to 48 h, bile from 0 h to 24 h, and plasma and brain tissue samples at 0.25, 1, 2 h after administration were collected.In vitro metabolism was incubated with rat liver microsomes and intestinal flora.The metabolites were analyzed and identified by the high-resolution HPLC-MS/MS technique.The liquid chromatography separation was carried out on ZORBAX SB-C18 column (4.6 mm×150 mm, 5 μm) with acetonitrile-0.1% formic acid solution as the mobile phase for gradient elution, the flow rate was 1.0 mL·min-1, and column temperature was 25 ℃.The mass spectra were obtained in positive and negative ion mode with electrospray ionization (ESI), the scanning range was m/z 50-1 200.The relative molecular weight was determined according to the quasi-molecular ion peaks.The structures of metabolites were elucidated by comparing the data with literature data, including main ion peaks, UV spectrum and HPLC retention time information. Result::A total of 17 metabolites were identified in each sample, including 11 phase Ⅰ metabolites and 6 phase Ⅱ metabolites.The pathways to these metabolites were hydroxylation, demethylation, dehydrogenation, sulfation and glucuronide conjugation. Conclusion::Coptisine can produce metabolic reaction of phase Ⅰ and phase Ⅱ in rat, and metabolites are predominantly present in urine, and the main metabolic site is liver.Coptisine is poorly absorbed and rarely metabolized in gastrointestinal tract, so it is mostly excreted through feces by prototype.This experiment can provide material basis for the pharmacodynamics and pharmacology of coptisine.
