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N-hydroxyphenacetin, a new urinary metabolite of phenacetin in the rat
journal contribution
posted on 2023-05-18, 12:07 authored by Stuart McLeanStuart McLean, Noel DaviesNoel Davies, Watson, H, Favretto, WA, Bignall, JCN-Hydroxyphenacetin has been found in the urine of rats dosed with phenacetin, extending previous reports that phenacetin is N-hydroxylated by liver microsomes in vitro. After an oral dose of phenacetin (500 mg/kg) urine was collected for 24 hr, conjugates hydrolyzed with extract of Helix pomatia, and the metabolites extracted with dichloromethane and treated with diazomethane. Methylation of N-hydroxyphenacetin produced a stable derivative, N-methoxyphenacetin, which was separated from most other metabolites by thin layer chromatography. Identification of N-methoxyphenacetin was by combined gas chromatography-mass spectrometry and comparison with the synthetic reference compound. Quantification by gas chromatography with flame-ionization detection showed that 0.023% of the dose of phenacetin was recovered from urine as N-hydroxyphenacetin. It is probable that this value considerably underestimates the extent of phenacetin N-hydroxylation in vivo, inasmuch as N-hydroxyphenacetin is known to be rapidly degraded in biological systems.
History
Publication title
Drug Metabolism and DispositionVolume
9Pagination
255-260ISSN
0090-9556Department/School
School of Pharmacy and PharmacologyPublisher
Amer Soc Pharmacology Experimental TherapeuticsPlace of publication
9650 Rockville Pike, Bethesda, USA, Md, 20814-3998Repository Status
- Restricted