title: In vivo screening of glutathione related detoxification products in the early state of drug development.
abstract: Glutathione (GSH) adducts and consecutive degradation products thereof are indications of reactive intermediates during drug metabolism. As demonstrated with the analgesic SX-PP 16 (4-amino-3,5-dibromacetanilide), however, interactions of a drug with GSH can be detected by labelling the GSH-stores with labelled cysteine, and consecutive administration of the unlabelled drug even at therapeutic doses. The GSH-adducts are sensitively and specifically traced by HPLC, applying column-switching and a combination of diode-array- and radioactivity detection. This approach seems to be much more sensitive than a classical GSH-depletion study. The structure of the main metabolite of SX-PP 16 (46% of urinary excretion) was elucidated as 3-bromo-4-amino-5-mercapturyl-acetanilid.
mesh_terms: D000083:Acetanilides / Q000378:metabolism*; D000818:Animals; D002250:Carbon Radioisotopes; D003545:Cysteine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D008658:Inactivation, Metabolic; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000083:Acetanilides; D002250:Carbon Radioisotopes; C053128:4-amino-3,5-dibromoacetanilide; D005978:Glutathione; D003545:Cysteine