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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 (79/81Br) 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.
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.
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).
Acknowledgements
Dr. J. Castro-Perez is thanked for discussions and technical expertise.
Declaration of interest
The Royal Society of Chemistry (Analytical Division), EPSRC, and AstraZeneca are acknowledged for the financial support to C. J. Duckett.