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

Research output: Contribution to journalArticle

70 Citations (Scopus)

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 - 1980
Externally publishedYes

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Epoxy Compounds
Acetaminophen
Metabolites
Epoxide Hydrolases
Gas Chromatography-Mass Spectrometry
Ascorbic Acid
Glutathione
Proteins
Ions
Hydrolases
3-hydroxyacetaminophen
Gas chromatography
Mass spectrometry
Substrates

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

3-Hydroxyacetaminophen : A microsomal metabolite of acetaminophen. Evidence against an epoxide as the reactive metabolite of acetaminophen. / Hinson, J. A.; Pohl, L. R.; Monks, Terrence; Gillette, J. R.; Guengerich, F. P.

In: Drug Metabolism and Disposition, Vol. 8, No. 5, 1980, p. 289-294.

Research output: Contribution to journalArticle

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