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题名: Ultra-performance liquid chromatographic-electrospray mass spectrometric determination (UPLC-ESI-MS) of O-demethylated metabolite of paeonol in vitro: Assay development, human liver microsome activities and species differences
作者: Liu, Hui-Xin1, 2;  Hu, Ying1;  He, Yu-Qi3;  Liu, Yong1;  Li, Wei1, 2;  Yang, Ling1
关键词: Ultra-performance liquid chromatography ;  Paeonol ;  Human liver microsomes ;  O-Demethylation ;  Enzyme kinetics ;  Species differences
刊名: TALANTA
发表日期: 2009-10-15
DOI: 10.1016/j.talanta.2009.06.018
卷: 79, 期:5, 页:1433-1440
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Physical Sciences
类目[WOS]: Chemistry, Analytical
研究领域[WOS]: Chemistry
英文摘要: A simple and sensitive method for determination of the O-demethylation activity of rat. dog, minipig. and human liver micrsomes toward paeonol using ultra-performance liquid chromatography with mass detection (UPLC-MS) has been developed. The method uses chemically synthesized O-demethylated metabolite of paeonol (2,4-dihydroxyacetophenone, DHA) as a standard for method validation. Validation was done with respect to specificity, linearity, detection limit, recovery, stability, precision and accuracy. The chromatographic separation was achieved on a UPLC BEH C(18) column (50 mm x 2.1 mm i.d., 1.7 mu m), with phase of acetonitrile-water (ratio 30:70). Selective ion reaction (SIR) monitor was specific for paeonol, DHA and I.S. The method was specific since there were no interference peaks from the reaction matrix. The calibration curve for DHA was linear from 0.5-100 mu M with r(2) = 0.9999. The newly developed method has good precision and accuracy. The method was successfully used to determine the kinetics of DHA activities toward paeonol in liver microsomes from different species. Dog liver microsomes (DLMs) were the most active in paeonol O-demethylation (709.7 pmol/min/mg protein) followed by rat liver microsomes (RLMs) (579.6 pmol/min/mg protein), HLMs (569.3 pmol/min/mg protein), and then minipig liver microsomes (PLMs) (417.3 pmol/min/mg protein). The developed method was appropriated for rapid screening paeonol O-demethylation activity in liver microsomes from different species. (C) 2009 Elsevier B.V. All rights reserved.
关键词[WOS]: RISK-ASSESSMENT ;  CYTOCHROME-P450 ENZYMES ;  INHIBITION ;  DRUGS ;  RAT ;  PHARMACOKINETICS ;  GLUCURONIDATION ;  OXIDATION ;  ADDUCT
语种: 英语
WOS记录号: WOS:000269288400037
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/141303
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China
2.Chinese Acad Sci, Grad Univ, Beijing, Peoples R China
3.Shanghai Univ Tradit Chinese Med, Shanghai, Peoples R China

Recommended Citation:
Liu, Hui-Xin,Hu, Ying,He, Yu-Qi,et al. Ultra-performance liquid chromatographic-electrospray mass spectrometric determination (UPLC-ESI-MS) of O-demethylated metabolite of paeonol in vitro: Assay development, human liver microsome activities and species differences[J]. TALANTA,2009,79(5):1433-1440.
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