title: The metabolism of 4-bromoaniline in the bile-cannulated rat: application of ICPMS ((79/81)Br), HPLC-ICPMS & HPLC-oaTOFMS.
abstract: 1. An excretion balance study was performed following i.p. administration of 4-bromoaniline (50 mg kg(-1)) to bile-cannulated rats, using bromine-detected ((79/81)Br) ICPMS for quantification. Approximately 90% of the dose was recovered in urine (68.9 ± 3.6%) and bile (21.4 ± 1.4%) by 48 h post-administration. 2. HPLC-ICPMS ((79/81)Br) was used to selectively detect and profile the major urinary and biliary-excreted metabolites and determined that the 0-12 h urine contained at least 21 brominated metabolites with 19 bromine-containing peaks observed in the 6-12 h bile samples. 3. The urinary and biliary metabolites were subsequently profiled using HPLC-oaTOFMS. By exploiting the distinctive bromine isotope pattern ca. 60 brominated metabolites were detected in the urine in negative electrospray ionisation (ESI) mode while bile contained ca. 21. 4. While a large number of bromine-containing metabolites were detected, the profiles were dominated by a few major components with the bulk of the 4-bromoaniline-related material in urine accounted for by 4-bromoanaline O-sulfate (∼75% of the total by ICPMS, 84% by TOFMS). In bile a hydroxylated N-acetyl compound was the major metabolite detected, forming some ∼65% of the 4-bromoaniline-related material by ICPMS (37% by TOFMS).
authors.affiliation: Biomedical Research Centre, Sheffield Hallam University , Sheffield , UK .
authors.forename: Catherine
authors.initials: C
authors.lastname: Duckett
authors.forename: Michael
authors.initials: M
authors.lastname: McCullagh
authors.forename: Christopher
authors.initials: C
authors.lastname: Smith
authors.forename: Ian D
authors.initials: ID
authors.lastname: Wilson
mesh_terms: D000814:Aniline Compounds / Q000378:metabolism* / Q000652:urine*; D000818:Animals; D001646:Bile / Q000378:metabolism*; D001966:Bromine / Q000652:urine*; D002404:Catheterization; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017208:Rats, Wistar; D016482:Urinalysis
chemical_list: D000814:Aniline Compounds; C023621:4-bromoaniline; D001966:Bromine
keywords: Aniline metabolism; HPLC-ICPMS; HPLC-MS; bromine detection; bromine-based excretion balance study
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