II. Novel deaminated sulfadiazine metabolites in neonatal calf tissue,plasma, and urine following oral treatment with 14C-sulfadiazine

Demonstration of the efficacy of Tribrissen® [trimethoprim(TMP): sulfadiazine(SDZ), 1:5] for treatment of calf scours led to a study of the disposition of ¹⁴C-SDZ in the neonatal calf. Two healthy male calves (～40 kg) received orally one Tribrissen® bolus [¹⁴C-SDZ (1.0 g):TMP (0.2 g)] each for five consecutive days. The calves were killed on day 14 after the last dose. Mean total SDZ-related residues were 0.04 ppm (muscle), 0.16 ppm (kidney) and 0.31 ppm (liver) on day 14. Intact SDZ was undetectable on day 14 in all three tissues. Two-dimensional TLC autoradiograms of tissue, plasma and urine extracts revealed the presence of SDZ, N⁴-acetyl SDZ, 4-hydroxy-SDZ, N⁴-acetyl-4-hydroxy SDZ and two novel metabolites that were identified by NMR and mass spectral analyses to be 2-benzenesulfonamidopyrimidine and 2-benzenesulfonamido-4-hydroxypyrimidine. Most of the SDZ dose (87%) was recovered in the urine with SDZ and N⁴-acetyl SDZ accounting for 16 and 42% of the dose. The other four compounds accounted for <5% of the dose. The data from this study indicate that assays that rely on the presence of the N⁴-amino group, such as the Bratton-Marshall procedure, measure only part of the SDZ-related tissue residues in neonatal calves.