Formation of a diazonium cation intermediate in the metabolism of sulphamethazine to desaminosulphamethazine in the rat

Abstract

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.