Structure Elucidation of Novel Metabolites of Gemfibrozil in Dog: Conjugation Reaction of Conjugated Metabolites
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- ISHIKAWA Minoru
- Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd. Department of Biotechnology, Faculty of Engineering, Tottori University
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- HONDA Tomoyo
- Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.
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- YOSHII Hidefumi
- Department of Biotechnology, Faculty of Engineering, Tottori University
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- IKEDA Toshihiko
- Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.
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- IWABUCHI Haruo
- Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd.
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Abstract
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.
Journal
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- Journal of the Mass Spectrometry Society of Japan
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Journal of the Mass Spectrometry Society of Japan 52 (1), 21-28, 2004
The Mass Spectrometry Society of Japan
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Details 詳細情報について
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- CRID
- 1390001206492888448
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- NII Article ID
- 10011944441
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- NII Book ID
- AN0010555X
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- COI
- 1:CAS:528:DC%2BD2cXislOkuro%3D
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- ISSN
- 18804225
- 18843271
- 13408097
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- NDL BIB ID
- 6845382
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed