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 metabolites in 0- to 24-hr excreta were CP-oxamic acid and CP-alcohol, which together accounted for about one-third of the radioactivity therein. The remainder was due to unchanged CP (15% dose), CP-base (5% dose), and various metabolites representing <4% dose each. Among these, CP-glucuronide and CP-sulfate have been previously isolated in mammals. In addition to these metabolites, several previously unreported in vivo CP biotransformation products were identified in this study by HPLC and MS 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. Besides these formally identified compounds, the CP-phosphate structure was tentatively assigned to a conjugate metabolite resistant to beta-glucuronidase and sulfatase hydrolysis. The possible origin of these metabolites is discussed extensively.