Formation of a diazonium cation intermediate in the metabolism of sulphamethazine to desaminosulphamethazine in the rat.
14C-Sulphamethazinediazonium tetrafluoroborate (14C-SDTFB) when orally administered to rats was converted primarily to 14C-labelled desaminosulphamethazine (desaminosulmet) and methanol-insoluble residues in the gastrointestinal tract (gut). 14C-labelled sulphamethazine (sulmet), N4-acetylsulmet, the N4-glucose conjugate of sulmet and other unidentified products were also observed in the tissues and urine of rats given 14C-SDTFB. 2. When 14C-sulmet, nitrite and dimethylaniline were simultaneously administered to a rat by the oral route, one of the 14C-labelled products formed in the stomach was isolated and identified as 4-dimethylaminophenyl [4-(N-4,6-dimethyl-2-pyrimidinyl)sulphamidophenyl] diazene, providing evidence that 14C-sulmet was diazotized in the stomach of the animal. 3. SDTFB was weakly mutagenic when evaluated by the Ames test. 4. The methanol-insoluble 14C-labelled residues in the gut of rats dosed orally with 14C-SDTFB and 14C-sulmet + nitrite were partially converted to 14C-labelled desaminosulmet, sulmet, N4-acetylsulmet and other unidentified products when fed to recipient rats.
D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D006224:Cricetinae; D003979:Diazonium Compounds / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D009153:Mutagens; D009573:Nitrites / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013418:Sulfamethazine / Q000031:analogs & derivatives* / Q000378:metabolism*; D014018:Tissue Distribution; D000096926:Benzenesulfonamides
D000814:Aniline Compounds; D003979:Diazonium Compounds; D009153:Mutagens; D009573:Nitrites; D013418:Sulfamethazine; C015157:N,N-dimethylaniline; C028503:desaminosulfamethazine; D000096926:Benzenesulfonamides