Metabolism of 3-chloro-4-fluoroaniline in rat using [14C]-radiolabelling, 19F-NMR spectroscopy, HPLC-MS/MS, HPLC-ICPMS and HPLC-NMR

DUCKETT, Catherine, LINDON, John, WALKER, Heather, ABOU-SHAKRA, Fadi, WILSON, Ian and NICHOLSON, Jeremy (2006). Metabolism of 3-chloro-4-fluoroaniline in rat using [14C]-radiolabelling, 19F-NMR spectroscopy, HPLC-MS/MS, HPLC-ICPMS and HPLC-NMR. Xenobiotica, 36 (1), 59-77.

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Abstract

The metabolic fate of 3-chloro-4-fluoroaniline was investigated in rat following intraperitoneal (i.p.) administration at 5 and 50 mg kg−1 using a combination of HPLC-MS, HPLC-MS/MS, 19F-NMR spectroscopy, HPLC-NMR spectroscopy and high-pressure liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS) with 35Cl and 34S detection. The metabolism of 3-chloro-4-fluoroaniline at both doses was rapid and extensive, to a large number of metabolites, with little unchanged compound excreted via the urine. Dosing at 5 mg kg−1 with [14C]-labelled compound enabled the comparison of standard radioassay analysis methods with 19F-NMR spectroscopy. 19F-NMR resonances were only readily detectable in the 0–12 h post-dose samples. Dosing at 50 mg kg−1 allowed the facile and specific detection and quantification of metabolites by 19F-NMR spectroscopy. Metabolite profiling was also possible at this dose level using HPLC-ICPMS with 35Cl-specific detection. The principal metabolites of 3-chloro-4-fluoroaniline were identified as 2-amino-4-chloro-5-fluorophenyl sulfate and 2-acetamido-4-chloro-5-fluorophenyl glucuronide. N-acetylation and hydroxylation followed by O-sulfation were the major metabolic transformations observed.

Item Type:	Article
Uncontrolled Keywords:	3-Chloro-4-fluoroaniline, HPLC-ICPMS, HPLC-MS, 14C-radiolabelling, 19F-NMR, aniline metabolism
Research Institute, Centre or Group - Does NOT include content added after October 2018:	Biomedical Research Centre
Departments - Does NOT include content added after October 2018:	Health and Well-being > Department of Bioscience
Identification Number:	https://doi.org/10.1080/00498250500489927
Page Range:	59-77
Depositing User:	Catherine Duckett
Date Deposited:	17 Jan 2018 14:49
Last Modified:	18 Mar 2021 16:31
URI:	https://shura.shu.ac.uk/id/eprint/18194

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