@article {McLean255, author = {S McLean and N W Davies and H Watson and W A Favretto and J C Bignall}, title = {N-hydroxyphenacetin, a new urinary metabolite of phenacetin in the rat.}, volume = {9}, number = {3}, pages = {255--260}, year = {1981}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {N-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 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.}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/9/3/255}, eprint = {https://dmd.aspetjournals.org/content/9/3/255.full.pdf}, journal = {Drug Metabolism and Disposition} }