Are Multimetabolite Methods Fit-For-Purpose for Supporting Toxicology Studies?

The measurement of parent drug in biological samples is an integral part of the drug-development process from discovery support through to late phase clinical development. At some point during this process it may also be necessary to measure metabolites of the drug. The regulatory guidelines on metabolite safety testing outline metabolite exposure data that is required to support drug registration. There are also a number of publications that describe strategies for validating bioanalytical methods used to quantify metabolites based on the development status of the drug. Despite current regulatory and scientific thinking on this subject, there still seems to be a consensus in parts of the industry that drug metabolites should be measured whenever possible, provided that it is technically feasible to do so, rather than basing this decision on the development requirements of the drug. One consequence of this strategy is that often several metabolites are quantified when supporting early development studies (e.g., regulatory toxicology studies) using bioanalytical methods that have been fully validated to measure all the metabolites. This approach may be regarded as a questionable use of resources at a time when a more targeted approach to drug-development is probably a better option.