Simultaneous determination of metformin and vildagliptin in human plasma by a HILIC–MS/MS method

•HILIC–LC–MS/MS for simultaneous determination of metformin and vildagliptin in plasma.•Quantification of metformin and vildagliptin in plasma for therapeutic drug monitoring.•A tool for clinical monitoring metformin and vildagliptin.

The objective of this work was to develop and validate a HILIC–MS/MS method for the simultaneous determination of metformin and vildagliptin in human plasma. Chromatographic separation was achieved using an Atlantis HILIC Silica 150-mm × 2.1-mm, 3-μm particle size column maintained at 40 °C. The isocratic mobile phase consisted of 20% water and 80% acetonitrile/water solution 95:5 (v/v), containing both 0.1% formic acid and 3 mM ammonium formate. The flow rate was maintained at 400 μL min−1. Data from validation studies demonstrated that the new method is highly selective, sensitive (limits of detection <1.5 ng mL−1) and free of matrix and residual effects. The new method was also precise (RSD < 9.0%), accurate (RE < 11.2%) and linear (r ≥ 0.99) over the ranges of 5–500 ng mL−1 for each compound. The developed method was successfully applied to determine metformin and vildagliptin in plasma volunteers who orally received a single dose of metformin (850 mg), vildagliptin (50 mg) or drug association (metformin 850 mg + vildagliptin 50 mg). The new method can thus also be used as a tool for the clinical monitoring of metformin and vildagliptin.