title: 19F-NMR and directly coupled HPLC-NMR-MS investigations into the metabolism of 2-bromo-4-trifluoromethylaniline in rat: a urinary excretion balance study without the use of radiolabelling.
abstract: 1. The metabolic fate and urinary excretion of 2-bromo-4-trifluoromethylaniline has been studied in rat using 19F-NMR spectroscopic and directly coupled HPLC-NMR-MS methods. The compound was dosed to Sprague-Dawley rats (50 mg kg-1, i.p.) and urine collected over 0-8, 8-24 and 24-48 h post-dosing. 2. A total urinary recovery of 53.5 +/- 7.0% of the dose was achieved up to 48 h after dosing. The major metabolite in the urine was identified as 2-amino-3-bromo-5-trifluoromethylphenylsulphate accounting for a total of 35.7 +/- 6.2% of the dose. 3. Further metabolites detected were 2-bromo-4-trifluoromethylphenylhydroxylamine-1V-glucuronide (9.7 +/- 0.2% of the dose), 2-bromo-4-trifluoromethylaniline-N-glucuronide (3.0 +/- 0.3%) and 2-amino-3-bromo-5-trifluoromethylphenylglucuronide (2-St 0-4). Minor metabolites, including 2-bromo-4-trifluoromethylphenylhydroxylamine-O-glucuronide, 2-amino-3-bromo-5-trifluoromethylphenol and 2-bromo-4-trifluoromethylphenylsulphamate, in total accounted for 2.3 +/- 0.9% of the dose. 4. Directly coupled HPLC-NMR-MS and 19F-NMR spectroscopy proved to be efficient techniques for the unequivocal and rapid determination of the urinary metabolic fate and excretion balance of fluorinated xenobiotics without the need for radiolabelling.
authors.affiliation: Department of Chemistry, Birbeck College, University of London, UK.
authors.forename: G B
authors.initials: GB
authors.lastname: Scarfe
authors.forename: B
authors.initials: B
authors.lastname: Wright
authors.forename: E
authors.initials: E
authors.lastname: Clayton
authors.forename: S
authors.initials: S
authors.lastname: Taylor
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: D000814:Aniline Compounds / Q000378:metabolism* / Q000652:urine; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D016719:Radioimmunodetection; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000814:Aniline Compounds; C112856:2-bromo-4-trifluoromethylaniline