One goal of metabolomics is to define and monitor the entire metabolite complement of a cell, while it is still far from reach since systematic and rapid approaches for determining the biotransformations of newly discovered metabolites are lacking. For drug development, such metabolic biotransformation of a new chemical entity (NCE) is of more interest because it may profoundly affect its bioavailability, activity and toxicity profile. The use of in silico methods to predict the site of metabolism (SOM) in phase I cytochromes P450-mediated reactions is usually a starting point of metabolic pathway studies, which may also assist in the process of drug/lead optimization.