The metabolism of 4-trifluoromethoxyaniline and [13C]-4-trifluoromethoxyacetanilide in the rat: detection and identification of metabolites excreted in the urine by NMR and HPLC-NMR.
A combination of 19F, 1H NMR and HPLC-NMR spectroscopic approaches have been used to quantify and identify the urinary-excreted metabolites of 4-trifluoromethoxyaniline (4-TFMeA) and its [13C]-labelled acetanilide following i.p. administration at 50 mg/kg to rats. The major metabolite excreted in the urine for both compounds was a sulphated ring-hydroxylated metabolite (either 2- or 3-trifluoromethyl-5-aminosulphate) which accounted for approximately 32.3% of the dose following the administration of 4-TFMeA and approximately 29.9% following dosing of the acetanilide. The trifluoromethoxy-substituent appeared to be metabolically stable, with no evidence of O-detrifluoromethylation. There was no evidence of the excretion of N-oxanilic acids in urine, of the type seen with 4-trifluoromethylaniline.
Tugnait
M
M
Biological Chemistry, Sir Alexander Fleming Building, Imperial College of Science, Technology and Medicine, South Kensington, SW72AZ, London, UK.
Lenz
E M
EM
Phillips
P
P
Hofmann
M
M
Spraul
M
M
Lindon
J C
JC
Nicholson
J K
JK
Wilson
I D
ID
D000083:Acetanilides / Q000032:analysis / Q000378:metabolism*; D000814:Aniline Compounds / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001192:Arylsulfatases / Q000737:chemistry; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes; D005966:Glucuronidase / Q000737:chemistry; D006868:Hydrolysis; D007274:Injections, Intraperitoneal; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017207:Rats, Sprague-Dawley
C461652:4-trifluoromethoxyacetanilide; D000083:Acetanilides; D000814:Aniline Compounds; D005462:Fluorine Radioisotopes; C461651:4-trifluoromethoxyaniline; D001192:Arylsulfatases; D005966:Glucuronidase