title: UPLC-MS, HPLC-radiometric, and NMR-spectroscopic studies on the metabolic fate of 3-fluoro-[U-14C]-aniline in the bile-cannulated rat.
abstract: 1. A study of the rates and routes of excretion of 3-fluoro-[U-(14)C]aniline following intraperitoneal administration to male bile-cannulated rats by liquid scintillation counting (LSC) gave a total recovery of approximately 90% in the 48 h following dosing, with the majority of the dose being excreted in the urine during the first 24 h (approximately 49%). 2. The total recovery as determined by (19)F-nuclear magnetic resonance ((19)F-NMR) was approximately 49%, with the majority of the dose excreted in the first 24 h (approximately 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 approximately 21 metabolites of 3-fluoroaniline (3-FA) with six of these detected only in urine and four solely in bile. 5. (19)F-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 (19)F-NMR spectroscopy made metabolite profiling impractical for this biofluid. The major metabolite of 3-FA was identified as 2-fluoro-4-acetamidophenol-sulfate.
authors.affiliation: Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: Athersuch
authors.forename: J
authors.initials: J
authors.lastname: Castro-Perez
authors.forename: C
authors.initials: C
authors.lastname: Rodgers
authors.forename: J K
authors.initials: JK
authors.lastname: Nicholson
authors.forename: Ian D
authors.initials: ID
authors.lastname: Wilson
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D001646:Bile / Q000737:chemistry; D001652:Bile Ducts / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000652:urine; D002404:Catheterization; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D011874:Radiometry; D051381:Rats; D017208:Rats, Wistar; D012588:Scintillation Counting
chemical_list: D002250:Carbon Radioisotopes; C007742:3-fluoroalanine; D000409:Alanine