3-Hydroxyacetaminophen: A microsomal metabolite of acetaminophen. Evidence against an epoxide as the reactive metabolite of acetaminophen

J. A. Hinson, L. R. Pohl, T. J. Monks, J. R. Gillette, F. P. Guengerich

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

3-Hydroxyacetaminophen has been isolated and identified as a microsomal metabolite of acetaminophen. Analysis of the metabolite by gas chromatography-mass spectrometry revealed that the metabolite had a molecular ion and fragmentation pattern identical to that of authentic 3-hydroxyacetaminophen. Glutathione and ascorbic acid blocked covalent binding of reactive metabolite(s) to protein but did not block the formation of 3-hydroxyacetaminophen. Moreover, epoxide hydrolase did not block covalent binding of the reactive metabolite(s) to protein. Thus, the reactive metabolite apparently is not an epoxide substrate of the hydrolase, nor are 3-hydroxyacetaminophen and the reactive metabolites(s) formed from a common intermediate.

Original languageEnglish (US)
Pages (from-to)289-294
Number of pages6
JournalDrug Metabolism and Disposition
Volume8
Issue number5
StatePublished - Dec 15 1980

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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