PT  - JOURNAL ARTICLE
AU  - Graeme B. Scarfe
AU  - John C. Lindon
AU  - Jeremy K. Nicholson
AU  - Brian Wright
AU  - Eddie Clayton
AU  - Ian D. Wilson
TI  - Investigation of the Quantitative Metabolic Fate and Urinary Excretion of 3-Methyl-4-Trifluoromethylaniline and 3-Methyl-4-Trifluoromethylacetanilide in the Rat
DP  - 1999 Oct 01
TA  - Drug Metabolism and Disposition
PG  - 1171--1178
VI  - 27
IP  - 10
4099  - http://dmd.aspetjournals.org/content/27/10/1171.short
4100  - http://dmd.aspetjournals.org/content/27/10/1171.full
SO  - Drug Metab Dispos1999 Oct 01; 27
AB  - The urinary metabolites of 3-methyl-4-trifluoromethylaniline in the rat were characterized and quantified using a combination of19F NMR, HPLC-NMR (1H and 19F), and HPLC-mass spectrometry techniques. The major routes of metabolism were amine N-acetylation and methyl groupC-oxidation to the benzyl alcohol (with subsequent glucuronide conjugation) and further to the corresponding benzoic acid derivative. Quantitatively only a small proportion of the urinary metabolites contained the free amino group, and these were products ofortho-hydroxylation (2 and 6 position) with additional conjugation to form the ether sulfates and glucuronides. AnN-glucuronide of the parent compound was also identified. 3-Methyl-4-trifluoromethylacetanilide (13C-labeled in the acetyl group) gave virtually the same overall metabolite profile as 3-methyl-4-trifluoromethylaniline; however, a significant level of futile N-deacetylation and reacetylation occurred as ca. 50% of the excretedN-acetylated major metabolites contained no13C-label at the acetyl, having been replaced by an endogenous 12C-acetyl source. This level of futile deacetylation is the highest yet reported for a substituted aniline/acetanilide and indicates a high degree of electronic activation of the amino group toward the acetyltransferase enzymes in vivo. The American Society for Pharmacology and Experimental Therapeutics