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

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

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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
Publication statusPublished - 1980
Externally publishedYes

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ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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