文献类型：期刊文献

中文题名：超高效液相色谱-质谱联用法分析川陈皮素在大鼠体内的代谢产物

英文题名：Identification of metabolites of nobiletin in rats using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry

作者：徐玲玲[1];何芋岐[2];郭忻[3];卢艳花[4];王长虹[2];王峥涛[1,2]

机构：[1]中国药科大学生药学研究室,江苏南京211198;[2]上海中医药大学中药研究所,中药标准化教育部重点实验室,中药新资源与品质评价国家中医药管理局重点研究室,上海201210;[3]上海中医药大学中药学院,上海201210;[4]华东理工大学生物反应器工程国家重点实验室,上海200237

年份：2011

卷号：46

期号：12

起止页码：1483

中文期刊名：药学学报

外文期刊名：Acta Pharmaceutica Sinica

收录：MEDLINE(收录号：22375423);CSTPCD;;Scopus;北大核心:【北大核心2008】；CSCD:【CSCD2011_2012】；PubMed;

基金：上海-联合利华研究与发展基金资助(09540715800);上海市教育委员会创新团队第二期项目资助

语种：中文

中文关键词：川陈皮素;代谢产物;超高效液相色谱-质谱

外文关键词：nobiletin; metabolite; UPLC-MS/MS

摘要：采用超高效液相色谱-三重四级杆质谱联用(UPLC-MS/MS)技术分析了川陈皮素在大鼠体内的代谢产物。通过比较给药前后大鼠血浆、胆汁和尿液样品的总离子流色谱图,观察到川陈皮素的7个代谢产物。进一步通过综合分析代谢产物的色谱保留行为、一级和二级质谱信息,推定其中3个为I相代谢产物,分别为川陈皮素脱去一个和两个甲基而得。另外4个被推定为II相代谢产物,分别为I相代谢产物进一步通过硫酸化和葡糖醛酸化生成。上述产物中,4个Ⅱ相代谢产物属首次报道。结果提示了Ⅱ相代谢尤其是葡糖醛酸化在川陈皮素代谢通路中的重要作用,提示葡糖醛酸转移酶的基因多态性以及相关的药物相互作用引起的潜在的川陈皮素活性及毒副作用的变化值得进一步的关注。
In this study,metabolism of nobiletin in rats was studied using ultra-performance liquid chromatography coupled with tandem mass spectrometry（UPLC-MS/MS）.As a result,seven major metabolites were found in bile,urine and serum of rats.Three phase I products were assigned to be demethyl and di-demethyl products,and other four phase Ⅱ products were assigned to be glucuronic and sulfonic conjugates.The four phase Ⅱ metabolites were reported for the first time.Among the metabolites found in the present study,the glucuronic conjugates of demethyl-nobiletin played a predominant role in the metabolic pathway,indicating that its potential role for glucuronidation-related factors,such as gene polymorphism,drug-drug interaction,etc.,in changing the active and toxic effect of nobiletin and that it should be paid more attention in further development.