title: The metabolism of 2-trifluormethylaniline and its acetanilide in the rat by 19F NMR monitored enzyme hydrolysis and 1H/19F HPLC-NMR spectroscopy.
abstract: The urinary excretion profile and identity of the metabolites of 2-trifluoromethyl aniline (2-TFMA) and 2-trifluoromethyl acetanilide (2-TFMAc), following i.p. administration to the rat at 50 mg kg(-1), were determined using a combination of 19F NMR monitored enzyme hydrolysis, SPEC-MS and 19F/1H HPLC-NMR. A total recovery of approximately 96.4% of the dose was excreted into the urine as seven metabolites. The major routes of metabolism were N-conjugation (glucuronidation), and ring-hydroxylation followed by sulphation (and to a lesser extent glucuronidation). The major metabolites excreted into the urine for both compounds were a labile N-conjugated metabolite (a postulated N-glucuronide) and a sulphated ring-hydroxylated metabolite (a postulated 4-amino-5-trifluoromethylphenyl sulphate) following dosing of 2-TFMA. These accounted for approximately 53.0 and 31.5% of the dose, respectively. This study identifies problems on sample component instability in the preparation and analysis procedures.
authors.affiliation: Biological Chemistry, Sir Alexander Fleming Building, Imperial College of Science, Technology and Medicine, South Kensington, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Tugnait
authors.forename: E M
authors.initials: EM
authors.lastname: Lenz
authors.forename: M
authors.initials: M
authors.lastname: Hofmann
authors.forename: M
authors.initials: M
authors.lastname: Spraul
authors.forename: I D
authors.initials: ID
authors.lastname: Wilson
authors.forename: J C
authors.initials: JC
authors.lastname: Lindon
authors.forename: J K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D000083:Acetanilides / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D000814:Aniline Compounds / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005461:Fluorine / Q000032:analysis; D006859:Hydrogen / Q000032:analysis; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000083:Acetanilides; D000814:Aniline Compounds; D005461:Fluorine; D006859:Hydrogen; C023650:aniline