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学科主题: 药学
题名:
Characterization of the metabolism of sibiricaxanthone F and its aglycone in vitro by high performance liquid chromatography coupled with Q-trap mass spectrometry
作者: Song, Yuelin; Yang, Xiaojuan; Jiang, Yong; Tu, Pengfei
关键词: Sibiricaxanthone F ; 1,3,6-Trihydroxy-2,7-dimethoxyxanthone ; Metabolism ; Intestinal bacteria ; Liver microsomes ; LC-MS/MS
刊名: JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
发表日期: 2012-11-01
DOI: 10.1016/j.jpba.2012.06.038
卷: 70, 页:700-707
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Analytical ; Pharmacology & Pharmacy
研究领域[WOS]: Chemistry ; Pharmacology & Pharmacy
关键词[WOS]: POLYGALA-TENUIFOLIA ROOT ; XANTHONE GLYCOSIDES ; MANGIFERIN ; GLUCURONIDATION ; DERIVATIVES ; RATS
英文摘要:

To explain the low bioavailability of sibiricaxanthone F (SF) following oral administration and to predict its possible metabolites in vivo, the in vitro biotransformation of SF and its metabolic stability in intestinal bacteria (BI) were studied. The metabolism of SF and its aglycone (1,3,6-trihydroxy-2,7-dimethoxyxanthone, Xan) was characterized after incubation with human and rat liver microsomes (HLMs and RLMs). The chemical structures of the metabolites were tentatively identified on the basis of their mass profiles using high performance liquid chromatography coupled with an enhanced mass spectrometry-information dependent acquisition-enhanced product ion (EMS-IDA-EPI) scan mode on a hybrid triple quadrupole-linear ion trap mass spectrometer. The metabolic stability of SF in BI was determined using the multiple reaction monitoring (MRM) mode. As a result, five hydrolyzed metabolites (M1-M4 and Xan) were generated stepwise for SF when it was incubated with BI, whereas two demethylated products (M1 and M5) were detected for Xan in BI. The metabolic stability study of SF in BI revealed that the parent compound could be rapidly hydrolyzed by Bland that Xan, the main corresponding metabolite, increased rapidly. In RLMs and HLMs, two hydrolyzed metabolites (M2 and M3) mediated by CYP450 isoenzymes appeared for SF in the presence of an NADPH-regenerating system, whereas no metabolite was detected for Xan under the same conditions. One (M6) and three glucuronidated metabolites (M7-M9) were generated from SF and Xan, respectively, by phase II isoenzymes in liver microsomal proteins in the presence of uridine 5′-diphosphoglucuronic acid (UDPGA). Overall, the present study revealed that extensive first-pass elimination occurred for SF in intestinal bacteria and hepatic subcellular proteins in vitro, which could be one of the main reasons for the low bioavailability of SF; furthermore, the possible SF-related metabolites in rats and humans were elucidated to be mono-glucuronidated derivatives of Xan following oral administration of SF. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 985-2-102-113 ; 30873429 ; 2012ZX09301002-002
项目资助者: Ministry of Education of China ; National Natural Science Foundation of China ; National Key Technology R&amp ; D Program "New Drug Innovation" of China
WOS记录号: WOS:000309314600097
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52088
Appears in Collections:北京大学药学院_期刊论文

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作者单位: Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
Song, Yuelin,Yang, Xiaojuan,Jiang, Yong,et al. Characterization of the metabolism of sibiricaxanthone F and its aglycone in vitro by high performance liquid chromatography coupled with Q-trap mass spectrometry[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2012,70:700-707.
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