Biotransformation of valdecoxib by microbial cultures

Microbial biotransformations can be used to predict mammalian drug metabolism. The present investigation deals with microbial biotransformation of valdecoxib using microbial cultures. Thirty nine bacterial, fungal and yeast cultures are used to elucidate the biotransformation pathway of valdecoxib. A number of microorganisms metabolized valdecoxib to various levels to yield nine metabolites, which were identified by HPLC-DAD and LC-MS-MS analyses. HPLC analysis of biotransformed products indicated that majority of the metabolites are more polar than the substrate valdecoxib. Basing on LC-MS-MS analysis, the major metabolite was identified as hydroxymethyl metabolite of valdecoxib, while the remaining metabolites were produced by carboxylation, demethylation, ring hydroxylation, N-acetylation or combination of these reactions. The hydroxymethyl and carboxylic acid metabolites were known to produce in metabolism by mammals. From the results it can be concluded that microbial cultures particularly fungi can be used to predict mammalian drug metabolism.