A validated HPLC-MS/MS method for simultaneous determination of linagliptin and metformin in spiked human plasma coupled with solid phase extraction: Application to a pharmacokinetic study in healthy volunteers

This study is concerned with the development of an HPLC-MS/MS method for simultaneous quantification of linagliptin and metformin in spiked human plasma. The method was applied to evaluate the potential pharmacokinetic interactions between the cited drugs in healthy volunteers. Solid-phase extraction was applied using Strata™ X cartridge. Separation was carried out on Symmetry® C18 column using methanol: 10 mM ammonium formate buffer (containing 0.2 % formic acid) in a ratio of (95: 5, v/v) as mobile phase at flow rate 0.25 mL min-1. Quantification was performed with multiple reaction monitoring in positive ionization mode. The monitored transitions were set at m/z 473.24 → 419.94, 130.14 → 60.18 and 340.27 → 116.07 for linagliptin, metformin and alogliptin (internal standard), respectively. The method was validated according to FDA guidelines. The method showed excellent linearity over concentration ranges 0.25-10 and 25-2000 ng mL-1 for linagliptin and metformin, respectively. The validated HPLC-MS/MS method was successfully applied to pharmacokinetic study of linagliptin and metformin in healthy volunteers after oral administration of Jentadueto® tablets.Graphical abstract
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research