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学科主题: 药学
题名:
Evaluation of the effect of TM208 on the activity of five cytochrome P450 enzymes using on-line solid-phase extraction HPLC-DAD: A cocktail approach
作者: Lin, Wensi1; Zhang, Jianmei1; Ling, Xiaomei1,2; Yu, Ning1; Li, Jing1; Yang, Haisong1; Li, Runtao2; Cui, Jingrong2
关键词: Probe drug cocktail ; Online solid-phase extraction ; HPLC ; TM208 ; Rat plasma
刊名: JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
发表日期: 2013-04-01
DOI: 10.1016/j.jchromb.2013.01.031
卷: 923, 页:29-36
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemical Research Methods ; Chemistry, Analytical
研究领域[WOS]: Biochemistry & Molecular Biology ; Chemistry
关键词[WOS]: TANDEM MASS-SPECTROMETRY ; 3-CYANO-3,3-DIPHENYLPROPYL ESTER HYDROCHLORIDE ; INTERINDIVIDUAL VARIATIONS ; PHENOTYPING PROBES ; MAJOR METABOLITES ; DRUG-METABOLISM ; IN-VIVO ; LC-MS ; P450 ; RAT
英文摘要:

A rapid, simple, and sensitive on-line solid-phase extraction HPLC-DAD method for simultaneous evaluation of the activity of five CYP450 isoforms (CYP1A2, CYP2C19, CYP2D6, CYP2E1 and CYP3A4) in vivo has been developed and validated. The five specific probe substrates include caffeine (1A2),metoprolol (2D6), dapsone (3A4), omeprazole (2C19) and chlorzoxazone (2E1). Automated pre-purification of plasma and enrichment of analytes were performed using a C18 on-line solid-phase extraction cartridge. After being eluted from the cartridge, the analytes and the internal standard antipyrine were separated on a C18 RP analytical column and analyzed by DAD. The method was validated to quantify the concentration ranges of 0.05-50.0 mu g/ml for dapsone and omeprazole, 0.1-50.0 mu g/ml for caffeine and 0.2-50.0 mu g/ml for metoprolol and chlorzoxazone. The linearity (R-2) for all analytes tested was exceeded 0.99. The intra-day precision ranged from 0.29 to 13% and the inter-day precision ranged from 5.0 to 15%, respectively. The intra-day and inter-day accuracy were between 86.7% and 113.6%. The extraction recoveries were in the range 82.8-109.9% for all the analytes and internal standard antipyrine. This method was successfully applied to evaluate the effects of TM208 on rat five CYP450 isoforms. (c) 2013 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 81072612 ; 7102107 ; K20110109 ; 20110001110021
项目资助者: National Natural Science Foundation ; Natural Science Foundation of Beijing ; Open Foundation of State Key Laboratory of Natural and Biomimetic Drugs ; Specialized Research Fund for the Doctoral Program of Higher Education of China
WOS记录号: WOS:000317148400005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61308
Appears in Collections:北京大学药学院_化学生物学系_期刊论文

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作者单位: 1.Peking Univ, Dept Pharmaceut Anal, Sch Pharmaceut Sci, Beijing 100871, Peoples R China
2.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China

Recommended Citation:
Lin, Wensi,Zhang, Jianmei,Ling, Xiaomei,et al. Evaluation of the effect of TM208 on the activity of five cytochrome P450 enzymes using on-line solid-phase extraction HPLC-DAD: A cocktail approach[J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,2013,923:29-36.
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