Fluorine NMR studies of the metabolism of flumecinol (3-trifluoromethyl-alpha-ethylbenzhydrol).

High-resolution and surface coil fluorine-19 NMR spectroscpies have been used to study the metabolism of the liver inducer 3-trifluoromethyl-alpha-ethylbenzhydrol (flumecinol) in rats. Although the fluorine chemical shift range exhibited by metabolites is small, it is possible to identify a number of metabolites or classes of metabolites by direct examination of urine samples. 3-Trifluoromethyl-4'-hydroxy-alpha-ethylbenzhydrol was confirmed as the primary metabolite at low doses (42 mg/kg). At higher doses other metabolites characterized by ring and side chain hydroxylation or further oxidation of the parent compound become apparent. NMR evidence for two previously unrecognized metabolites is described but these structures have not been identified. Studies of liver induction are reported that show that a single large dose of flumecinol exerts a substantial inducing effect on the number and types of metabolites formed after several hours postingestion. Examination of liver metabolism of the drug in vivo showed a single broad resonance, and it was not possible to obtained resolved signals for individual metabolites under the conditions of these experiments. However, nuclear Overhauser experiments showed that the materials detected in the in vivo experiments do not interact significantly with the macromolecular components of the liver.