Gas-phase rearrangement of the O-glucuronide of Vildagliptin forms product ion fragments suggesting wrongly an N-glucuronide.

The O -glucuronide of vildagliptin, a dipeptidyl peptidase 4 inhibitor (DPP-4), is a major metabolite in monkey and a minor metabolite in humans, rats and dogs. Its product ion spectrum shows fragments that can be only explained by an N -glucuronide. Biotransformation utilizing rat liver yielded mg amounts of the O -glucuronide and its structure was assigned unambiguously by NMR. The MS/MS spectrum of this compound was investigated in detail utilizing MSn and accurate mass spectrometers and was identical to the animal metabolite. Thus, the MS/MS fragments suggesting an N -glucuronide had to be formed by gas-phase rearrangement. This gas-phase rearrangement can be observed on QTOF and ion trap mass instruments. The literature on gas-phase rearrangements is reviewed.