UPLC-MS, HPLC-radiometric, and NMR-spectroscopic studies on the metabolic fate of 3-fluoro-[U-C-14]-aniline in the bile-cannulated rat

作者：Athersuch T J; Castro Perez J; Rodgers C; Nicholson J K; Wilson I D^*

来源：Xenobiotica, 2010, 40(7): 510-523.

DOI：10.3109/00498254.2010.483294

• 3-fluoroaniline
• aniline metabolism
• UPLC-MS
• H-1-NMR
• F-19-NMR

1. A study of the rates and routes of excretion of 3-fluoro-[U-C-14]aniline following intraperitoneal administration to male bile-cannulated rats by liquid scintillation counting (LSC) gave a total recovery of similar to 90% in the 48 h following dosing, with the majority of the dose being excreted in the urine during the first 24 h (similar to 49%).
2. The total recovery as determined by F-19-nuclear magnetic resonance (F-19-NMR) was similar to 49%, with the majority of the dose excreted in the first 24 h (similar to 41%). The comparatively low recovery in comparison to that obtained from LSC was due to matrix effects in bile and a contribution from metabolic defluorination.
3. High-performance liquid chromatography with radiometric profiling of urine and bile revealed a complex pattern of metabolites with the bulk of the dose excreted as a single peak.
4. Ultra-performance liquid chromatography-orthogonal acceleration time of flight mass spectrometry profiling also showed a complex pattern of metabolites, detecting similar to 21 metabolites of 3-fluoroaniline (3-FA) with six of these detected only in urine and four solely in bile.
5. F-19-NMR revealed the presence of the parent compound and 15 metabolites in urine collected during the first 24 h after-dosing. The matrix effects of bile on F-19-NMR spectroscopy made metabolite profiling impractical for this biofluid.
6. The major metabolite of 3-FA was identified as 2-fluoro-4-acetamidophenol-sulfate.

• 出版日期2010-7