Structure Elucidation of Novel Metabolites of Gemfibrozil in Dog: Conjugation Reaction of Conjugated Metabolites

• ISHIKAWA Minoru

  Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd. Department of Biotechnology, Faculty of Engineering, Tottori University

• HONDA Tomoyo

  Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.

• YOSHII Hidefumi

  Department of Biotechnology, Faculty of Engineering, Tottori University

• IKEDA Toshihiko

  Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.

• IWABUCHI Haruo

  Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.

抄録

After oral administration of ¹⁴C-labeled gemfibrozil to male dogs, ten metabolites of gemfibrozil, designated as dog metabolite (DM)-1, DM-2, DM-3, DM-4, DM-5-1, DM-5-2, DM-6, DM-7, DM-8, and DM-9, were detected in the urine. Structural analysis of these metabolites by mass spectrometry and tandem mass spectrometry in various ionization modes demonstrated that DM-1, DM-2, DM-3, DM-4, DM-5-1, DM-5-2, and DM-6 were previously unreported metabolites of gemfibrozil. With the exception of DM-8 and DM-9, the gemfibrozil metabolites in dog urine were conjugated metabolites produced by glucuronidation at the carboxylic acid group and the phenolic hydroxyl group generated metabolically or by sulfo-conjugation at the phenolic hydroxyl group. Interestingly, DM-1 and DM-2 were demonstrated to be unique, doubly conjugated forms of DM-9. In DM-1, glucuronidation had occurred at both the carboxylic acid group and phenolic hydroxyl group. In DM-2, sulfo-conjugation at the phenolic hydroxyl group and glucuronidation at the carboxylic acid group had occurred. Therefore, the dogs were found to possess enzymatic mechanisms that glucuronidate or sulfo-conjugate already conjugated metabolites, converting water-soluble metabolites to hydrophilic metabolites.

収録刊行物

• 質量分析

  質量分析 52 (1), 21-28, 2004

  一般社団法人 日本質量分析学会

キーワード

• Structural elucidation
• LC/MS/MS
• EI
• Gemfibrozil
• Drug metabolism

詳細情報

• CRID: 1390001206492888448
• NII論文ID: 10011944441
• NII書誌ID: AN0010555X
• DOI: 10.5702/massspec.52.21
• COI: 1:CAS:528:DC%2BD2cXislOkuro%3D
• ISSN: 18804225
• ISSN: 18843271
• ISSN: 13408097
• NDL書誌ID: 6845382
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I6845382
• Web Site: http://www.jstage.jst.go.jp/article/massspec/52/1/52_1_21/_pdf
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可