The metabolism of 4-bromoaniline in the bile-cannulated rat: application of ICPMS (79/81Br), HPLC-ICPMS & HPLC-oaTOFMS

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Duckett, Catherine ; McCullagh, Michael ; Smith, Christopher ; Wilson, Ian D (2015)
  • Publisher: Informa Healthcare
  • Journal: Xenobiotica; the Fate of Foreign Compounds in Biological Systems, volume 45, issue 8, pages 672-680 (issn: 0049-8254, eissn: 1366-5928)
  • Related identifiers: pmc: PMC4776724, doi: 10.3109/00498254.2015.1007491
  • Subject: HPLC-ICPMS | HPLC-MS | Aniline metabolism | bromine detection | Animal Pharmacokinetics and Metabolism | bromine-based excretion balance study

<p>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 (79/81Br) 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.</p>\ud \ud <p>2. HPLC-ICPMS (79/81Br) 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.</p>\ud \ud <p>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.</p>\ud \ud <p>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).</p>
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