Validated method for rapid inhibition screening of six cytochrome P450 enzymes by liquid chromatography-tandem mass spectrometry
文献类型：期刊论文
| 作者 | Li, Xiaoyan; Chen, Xiaoyan ; Li, Qiang; Wang, Linling; Zhong, Dafang
|
| 刊名 | JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
 |
| 出版日期 | 2007-06-01 |
| 卷号 | 852期号:1-2页码:128-137 |
| 关键词 | acetaminophem 4-hydroxytolbutamide 4'-hydroxymephenytoin dextrorphan 1'-hydroxymidazolam 3-methyoxymorphinan 6-hydroxychlorzoxazone |
| ISSN号 | 1570-0232 |
| DOI | 10.1016/j.jchromb.2007.01.006 |
| 文献子类 | Article |
| 英文摘要 | In vitro drug interaction data can be used in guiding clinical interaction studies, or, the design of new candidates. To make such a claim, it must be assured that the in vitro data obtained is confident. To meet this need, a rapid liquid chromatography-tandem mass spectrometry (LC/MSIMS) method has been validated and employed for routine screening of new chemical entities for inhibition of six major human cytochrome P450 (CYP) isoforms using cDNA-expressed CYPs. Probe substrates were used near the Michaelis-Menten constant (K.) concentration values for CYPIA2 (phenacetin), CYP2C9 (tolbutamide), CYP2C19 (S-mephenytoin), CYP2D6 (dextromethorphan) and CYP3A4 (midazolam and dextromethorphan). The major metabolites of CYP-specific probe substrates were quantified. The LC/MS/MS method was found to be accurate and precise within the linear range of 1.0-2000 ng/ml for each analyte in enzyme incubation mixture. The lower limit of quantification (LLOQ) was 1.0 ng/ml. The limit of detection (LOD) for the tested analytes was 0.48 ng/ml or better based on signal-to-noise ratio > 3. The inhibition potential of the six CYP isoforms has been evaluated using their known selective inhibitors. The 50% inhibitory concentrations (IC50 Values) measured by this method demonstrated high precision and are consistent with the literature values. (c) 2007 Elsevier B.V. All rights reserved. |
| WOS关键词 | PROBE-DOSING STRATEGY ; VITRO DRUG-INTERACTIONS ; IN-VITRO ; CYP3A4 ; METABOLITES ; MICROSOMES ; ASSAYS ; TESTS ; 3A4 ; 2E1 |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000247286700018 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273244]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhong, Dafang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Metab & Pharmacokinet Res, Shanghai 201203, Peoples R China 2.Shenyang Pharmaceut Univ, Shenyang 110016, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Xiaoyan,Chen, Xiaoyan,Li, Qiang,et al. Validated method for rapid inhibition screening of six cytochrome P450 enzymes by liquid chromatography-tandem mass spectrometry[J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,2007,852(1-2):128-137. |
| APA | Li, Xiaoyan,Chen, Xiaoyan,Li, Qiang,Wang, Linling,&Zhong, Dafang.(2007).Validated method for rapid inhibition screening of six cytochrome P450 enzymes by liquid chromatography-tandem mass spectrometry.JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,852(1-2),128-137. |
| MLA | Li, Xiaoyan,et al."Validated method for rapid inhibition screening of six cytochrome P450 enzymes by liquid chromatography-tandem mass spectrometry".JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 852.1-2(2007):128-137. |
入库方式： OAI收割
来源：上海药物研究所
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