A reflection on fit-for-purpose metabolite investigation at different stages of drug development

“The ability of preclinical species to form the relevant human metabolites remains a key deliverable of discovery metabolism work.” The identification of drug metabolites and their quantification has led to much discussion in recent years, mainly related to the publication of regulatory guidances on human metabolites and the basis for their toxicological evaluation [1,2]. Several key publications have stimulated and challenged the scientific community with regard to MIST strategies [3], analytical approaches to demonstrate the coverage of human relevant metabolites in preclinical species [4], the concept of a gradual investment in the validation of analytical methods for drug metabolites [5],...