Simultaneous quantitative analysis of retagliptin and its main active metabolite in human multiple matrices by liquid chromatography tandem mass spectrometry

Retagliptin is a dipeptidyl peptidase 4 (DPP-4) inhibitor which has proven efficacy and safety towards type 2 diabetes mellitus (T2DM). In order to investigate the pharmacokinetics of retagliptin and its main active metabolite, retagliptin acid, we developed liquid chromatography tandem mass spectrometry (LC-MS/MS) methods for the simultaneous determination of retagliptin and retagliptin acid in human plasma, urine and feces. The lower limit of quantification (LLOQ) for retagliptin and retagliptin acid is 0.1 ng mL−1 and 0.3 ng mL−1 in plasma, 5 ng mL−1 and 10 ng mL−1 in urine, and 1 ng mL−1 and 3 ng mL−1 in feces. The methods were fully validated and successfully applied in the pharmacokinetic study of humans after an oral administration of 100 mg retagliptin.