Urinary metabolites of halothane in man.
The urinary metabolites of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) were investigated in five individuals given trace doses (25 muCi), and in three individuals given large doses (1 mCi) of radioactively labeled 14C-halothane. The latter were donor subjects for heart transplant operations. Separation of the nonvolatile urinary metabolites of halothane was accomplished by chemical extraction, electrophoresis, ion-exchange and high-pressure liquid chromatography, and gas chromatography. Identification of the individual metabolites was by nuclear magnetic resonance and mass spectrometry. Three major metabolites were identified: trifluoroacetic acid, N-trifluoroacetyl-2-aminoethanol, and N-acetyl-S-(2-bromo-2-chloro-1,1-difluoroethyl)-L-cysteine. Smaller unidentified radioactive peaks were also found. The presence of both ethanolamide and cysteine conjugates of halothane is of concern. These urinary products imply the presence of reactive intermediates. The conjugation of such intermediates to proteins and phospholipids may give rise to the high-molecular-weight covalently bound metabolites demonstrated to be present in the liver following halothane anesthesia. Elucidation of the structures of the urinary metabolites provides information important to an understanding of halothane metabolism and its potential hepatotoxicity.
D001665:Binding Sites; D002250:Carbon Radioisotopes; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003545:Cysteine / Q000031:analogs & derivatives / Q000652:urine; D004983:Ethanolamines / Q000652:urine; D005463:Fluoroacetates; D005978:Glutathione / Q000378:metabolism; D006221:Halothane / Q000009:adverse effects / Q000378:metabolism*; D016027:Heart Transplantation; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D014019:Tissue Donors; D014184:Transplantation, Homologous; D014269:Trifluoroacetic Acid / Q000652:urine
D002250:Carbon Radioisotopes; D004983:Ethanolamines; D005463:Fluoroacetates; C011135:N-trifluoroacetyl-2-aminoethanol; D014269:Trifluoroacetic Acid; D005978:Glutathione; D003545:Cysteine; D006221:Halothane