Biotransformation of Albendazole by Cunninghamella blakesleeana:Influence of Incubation Time, Media, Vitamins and Solvents

Abstract

The present investigation was aimed at studying the effect of incubation period, media, vitamins and solvents on biotransformation of albendazole by Cunninghamella blakesleeana. The transformation was evaluated and identified by high performance liquid chromatography (HPLC) and the structures of the transformed products were assigned by liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis. The fungus was found to metabolize albendazole into albendazole sulfoxide (M1), albendazole sulfone (M2) and the N-methyl metabolite of albendazole sulfoxide (M3). Incubation period was found to influence the biotransformation significantly; 4 days was found to be optimum, but the effect was neither linear nor progressive. There was a significant effect of medium on the extent of biotransformation, with the highest substrate depletion produced by the glucose broth. The media also influenced qualitative metabolite formation. Presence of thiamine in the glucose media produced the maximum extent of transformation when compared to other vitamins studied. Dimethylformamide produced a higher extent of biotransformation. The fermentor was found to produce an increased level of biotransformation as compared to that obtained in shake flasks.