EVIDENCE FOR NEW METABOLIC PATHWAYS OF CHLORAMPHENICOL IN THE DUCK

Following subcutaneous administration of [H-3]chloramphenicol (CP) to duck, HPLC and TLC analyses showed that the two most important metabol ites in 0- to 24-hr excreta were CP-oxamic acid and CP-alcohol, which together accounted for about one-third of the radioactivity therein. T he remainder was due to unchanged CP (15% dose), CP-base (5% dose), an d various metabolites representing <4% dose each. Among these, CP-gluc uronide and CP-sulfate have been previously isolated in mammals. In ad dition to these metabolites, several previously unreported in vivo CP biotransformation products were identified in this study by HPLC and M S comparison with synthetic reference compounds. These new metabolites were unequivocally identified as 1-O-monoacetyl CP, CP-1,3-diacetate, N-acetyl CP-base, CP-oxamylglycine, and CP-oxamylethanolamine. Beside s these formally identified compounds, the CP-phosphate structure was tentatively assigned to a conjugate metabolite resistant to beta-glucu ronidase and sulfatase hydrolysis. The possible origin of these metabo lites is discussed extensively.