Labile Metabolites

The importance of ascertaining the possible presence of unstable metabolites at an early stage in the drug development process cannot be underestimated. Failure to detect labile metabolites could lead to costly delays to development. Very often, erratic or difficult to explain analytical or kinetic data provide clues to metabolite degradation, the most commonly encountered reaction being the conversion of a metabolite to parent drug. Examples of unstable glucuronide conjugates, N-oxides, alcohols and phenols abound in the literature. They are not easy to find, however, and have to be ‘mined’ by extensive searching. This report, by no means exhaustive, brings together the major examples according to substance class. Remedial action to avoid metabolite degradation is discussed, as well as a number of specific examples which cannot be categorised under the main substance classes.