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
Liu, Hui-Xin1,2; Hu, Ying1; He, Yu-Qi3; Liu, Yong1; Li, Wei1,2; Yang, Ling1
刊名talanta
2009-10-15
卷号79期号:5页码:1433-1440
关键词Ultra-performance liquid chromatography Paeonol Human liver microsomes O-Demethylation Enzyme kinetics Species differences
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.
WOS标题词science & technology ; physical sciences
类目[WOS]chemistry, analytical
研究领域[WOS]chemistry
关键词[WOS]risk-assessment ; cytochrome-p450 enzymes ; inhibition ; drugs ; rat ; pharmacokinetics ; glucuronidation ; oxidation ; adduct
收录类别SCI
语种英语
WOS记录号WOS:000269288400037
公开日期2015-11-17
内容类型期刊论文
源URL[http://159.226.238.44/handle/321008/141303]  
专题大连化学物理研究所_中国科学院大连化学物理研究所
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
推荐引用方式
GB/T 7714
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.
APA Liu, Hui-Xin,Hu, Ying,He, Yu-Qi,Liu, Yong,Li, Wei,&Yang, Ling.(2009).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.talanta,79(5),1433-1440.
MLA Liu, Hui-Xin,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".talanta 79.5(2009):1433-1440.
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