論文

査読有り
2004年3月

Determination of midazolam and its metabolite as a probe for cytochrome P450 3A4 phenotype by liquid chromatography-mass spectrometry

JOURNAL OF CHROMATOGRAPHY A
  • H Kanazawa
  • ,
  • A Okada
  • ,
  • E Igarashi
  • ,
  • M Higaki
  • ,
  • T Miyabe
  • ,
  • T Sano
  • ,
  • R Nishimura

1031
1-2
開始ページ
213
終了ページ
218
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.chroma.2003.12.039
出版者・発行元
ELSEVIER SCIENCE BV

This study demonstrated the analysis of midazolam and its metabolites by liquid chromatography-mass spectrometry (LC-MS) with a sonic spray ionization (SSI) interface. The analytical column was a YMC-Pak Pro C-18 (50 mm x 2.0 mm i.d.) using 10 mM ammonium acetate (pH 4.8)-methanol (1:1) at a flow rate of 0.2 ml min(-1). The drift voltage was 100 V. The sampling aperture was heated at 101degreesC and the shield temperature was 230 degreesC. The lower limits for the detection of midazolam and 1'-hydroxymidazolam were 26.3 and 112.76 pg injected, respectively. The calibration curves for midazolam and 1'-hydroxymidazolam were linear in the range of 0.1-5 mug ml(-1). Within-day relative standard deviations was less than 7%. The method was applied to the determination of midazolam in monkey plasma, and the analysis of midazolam and its metabolites in an in vitro study with recombinant cytochrome P450 (CYP) 3A4, This method is sufficiently sensitive and useful to elucidate the kinetics of midazolam metabolite formation. We also investigated the effect of propofol on the metabolism of midazolam using recombinant CYP3A4. Propofol competitively inhibited the metabolism of midazolam to 1'-hydroxymidazolam by CYP3A4. (C) 2004 Elsevier B.V All rights reserved.

リンク情報
DOI
https://doi.org/10.1016/j.chroma.2003.12.039
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000220030800025&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.chroma.2003.12.039
  • ISSN : 0021-9673
  • Web of Science ID : WOS:000220030800025

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