DISPOSITION OF ORAL [C-14] SULFATHIAZOLE IN SWINE

Disposition of oral sulfathiazole was studied in swine. Pigs were slaughtered 6, 12, 24, and 48 h after an oral dose of [C-14]sulfathiazole (two at each time period). Excretion of C-14 was rapid (>90% in 48 h), primarily via the urine. Metabolites isolated and characterized by H-1 NMR and FAB MS were N-4-acetylsulfathiazole from urine, kidney, liver, blood, and muscle; N-4-glucoside of sulfathiazole from muscle; and an apparent diconjugate from liver, a glucuronide of N-4-acetylsulfathiazole. Quantitation was accomplished by HPLC analysis of samples (extracts of tissue and urine) spiked with the reference compounds. Peaks corresponding to the retention time of the reference compounds were trapped and assayed for C-14. Sulfathiazole and N-4-acetylsulfathiazole were the principal C-14-labeled compounds in urine and kidney. If present, the glucoside or glucuronide represented <5% of the C-14 in urine. Liver and muscle contained significant amounts of sulfathiazole, N-4-acetylsulfathiazole, and N-4-glucoside of sulfathiazole. Quantitation of the diconjugate was not attempted. The amounts isolated suggest it was a minor metabolite; however, instability during isolation was apparent. On the basis of the results, liver, kidney, and urine are potential target tissues for a residue monitoring program and the nature of the metabolite present in the tissue must be considered when an assay procedure is selected.