Drug and metabolite stability studies
Stability evaluation of parent drug and metabolite formation in faecal incubations
In addition to monitoring the stability of synthesised metabolites in storage, Hypha can investigate stability of a drug or metabolites in a faecal environment as part of drug and metabolite stability studies.
Structural moieties of some drug compounds may be susceptible to chemical reaction in the gut environment, or to biotransformation by microbes in the intestine to gut-specific metabolites. This can be significant enough that resulting metabolites are absorbed and observed as circulating metabolites, as observed in the metabolism of the drug ozanimod in humans (Surapaneni et al., 2021).
Hypha can monitor stability of drugs or their metabolites in a faecal environment. This is performed over a time course comparing incubations in live and heat treated faecal samples and buffer, to check for reversion to the parent drug or further biotransformation. New metabolites can be isolated and their structures elucidated by NMR spectroscopy. Find out more about our gut metabolism capabilities.
Case study
In this case study, a previously uncharacterised major metabolite was detected in human plasma from SAD and MAD study samples to a 19% total abundance.
Hypha conducted a study to investigate whether this ring-rearranged metabolite could be made in the gut by dosing the parent drug in human fecal incubations under anaerobic conditions.
The major metabolite was produced under these conditions along with three other known circulating metabolites and the discovery of one new metabolite. Up to 25% conversion of the parent drug was observed after a 48h incubation.