Solving challenging drug metabolite projects
Some metabolites are not easy to access. Even if sufficient material can be isolated from biological matrices for definitive metID, getting hold of larger quantities for further testing is not always straightforward.
One such challenging project we completed for a US client involved the need to access hundreds of milligrams of three different metabolites; an N-glucuronide, a hydroxylated metabolite and an indirect O-glucuronide. By applying some of the tools in Hypha’s One-Stop Metabolite Shop, we were able to deliver these amounts. This involved application of late-stage chemical glucuronidation to prepare the N-glucuronide, a difficult chemical synthesis of the hydroxylated metabolite, and microbial biotransformation to produce the indirect O-glucuronide, as well as purification and structure elucidation by NMR.