Abstract: Abstract: Objective To develop a liquid chromatography-tandem mass spectrometry (LC-MS / MS) method for quantification of sitagliptin in human plasma, and to apply it for the pharmacokinetics study of sitagliptin in human. Methods The plasma sample was precipitated by CleanertPPT and sitagliptin-d4 was used as the internal standard (IS). Chromatographic separation was performed on a Diamonsil C18 column (100 mm×4.6 mm, 5 μm). Mobile phase consisted of methanol and a mixture of 10 mmol/L ammonium formate-methanol-formic acid (90∶10∶0.1) at a flow rate of 0.5 mL/min. The validation was performed in terms of selectivity, residue, linear range and lower limit of quantitation, precision and accuracy, matrix effects and recovery, and stability. The main pharmacokinetic parameters (Tmax, Cmax, AUC0-t and T1/2) were observed in healthy people after oral administration of sitagliptin tablets. Results Sitagliptin and sitagliptin-d4 (IS) were ionized with an ESI source and operated in positive ion mode. The detected ions were m/z 408.0→235.2 (sitagliptin) and m/z 412.1→239.0 (sitagliptin-d4). This validated LC-MS/MS method yielded a good linearity over the range of 0.5-1 000 μg/L (R2=0.99), and the lower limit of quantitation (LLOQ) was 0.5 μg/L. The intra and inter-assay precisions (RSD) were within the range of 0.83%~12.80%, and the accuracy (RE) was less than ± 10.0%. The pharmacokinetic parameters, Tmax, Cmax, AUC 0-t and T1/2 were (2.44±1.29) h, (375±138) μg/L, (2 915±585) h·μg/L and (11.10±2.41) h. Conclusion This LC-MS / MS method is simple, sensitive, rapid and suitable for pharmacokinetics study of sitagliptin in human being.

Key words: dipeptidyl-peptidase Ⅳ inhibitors, pharmacokinetics, Sitagliptin, liquid chromatography-tandem mass spectrometry, tandem mass spectrometry