Identification of Gemfibrozil Metabolites, Produced as Positional Isomers in Human Liver Microsomes, by On-line Analyses Using Liquid Chromatography/Mass Spectrometry and Liquid Chromatography/Nuclear Magnetic Resonance Spectroscopy

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Liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/nuclear magnetic resonance spectroscopy (LC/NMR) were applied to the identification of the positional isomers of gemfibrozil metabolites produced <i>in vitro</i> by human liver microsomes. Gemfibrozil was metabolized to two major oxidative metabolites (M1 and M2) by human liver microsomes in the presence of an nicotinamide adenine dinucleotide phosphate, reduced form (NADPH)-generating system. M1 and M2 were characterized as metabolites formed by the oxidation of the 2′,5′-dimethylphenoxy moiety, which has potentially 5 different positions for hydroxylation, based on the results of negative-ion tandem mass spectrometry in combination with those of accurate mass measurements by quadrupole time-of-flight mass spectrometry. Separation and identification of M1 and M2 were conducted by LC/NMR analyses at 500 MHz. An on-flow <sup>1</sup>H NMR analysis demonstrated that M1 was produced by hydroxylation at either the 2′-methyl group or the 5′-methyl group and M2 by hydroxylation at either the 3′-C or the 4′-C position of the aromatic ring. A stop-flow nuclear Overhauser effect spectroscopy (NOESY) analysis demonstrated that M1 and M2 were metabolites hydroxylated at the 5′-methyl group and the 4′-C position of the aromatic ring, respectively.

収録刊行物

  • 質量分析 = Mass spectroscopy

    質量分析 = Mass spectroscopy 52(5), 277-283, 2004-10-01

    一般社団法人 日本質量分析学会

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各種コード

  • NII論文ID(NAID)
    10013736872
  • NII書誌ID(NCID)
    AN0010555X
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13408097
  • NDL 記事登録ID
    7132533
  • NDL 雑誌分類
    ZP4(科学技術--化学・化学工業--分析化学)
  • NDL 請求記号
    Z17-213
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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