Focus Feature - Deuterated Metabolites

Clients are often in need of labelled metabolites, in particular, deuterated metabolites for use as internal standards. With this in mind, we look at how Hypha make deuterated metabolites, illustrated using case studies where biotransformation and late-stage chemical synthesis techniques were employed.

In addition to the typical client projects featured in the case study, we exemplify one of the biotransformation routes to making deuterated metabolites using oxidation of flurbiprofen as a model substrate.

Screening of flurbiprofen against a panel of PolyCYPs^® enzymes and microbes resulted in several products. A fungal biotransformation produced the major metabolite 4’-hydroxyflurbiprofen with almost complete conversion. The correct product was confirmed by NMR spectroscopy of the purified metabolite.

Metabolism of flurbiprofen-d3 also results in hydroxylation at the same position by the same enzymes and microbes, albeit the fungal biotransformation proceeding more slowly than observed with the non-deuterated drug. It is expected that some biotransformation processes may be affected by deuteration at sites of metabolism in compounds but we haven't yet encountered a project where this was an issue in making the deuterated metabolite.

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