Pharmacokinetic and protein binding profile of peptidomimetic DPP-4 inhibitor – Teneligliptin in rats using liquid chromatography–tandem mass spectrometry

• A simple bioanalytical LC–MS based method for analysis of teneligliptin in rats was developed.
• The method was found to be linear in the range of 0.5–1000 ng/mL.
• Applied to pharmacokinetic and protein binding study.

The aim of the present study is to explore pharmacokinetic and protein binding characteristics of a novel dipeptidylpeptidase-4 (DPP-4) inhibitor, teneligliptin in rats using an ultra high performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC–QTOF-MS). It is required for demonstrating the high protein binding nature of teneligliptin which can be extended for drug repositioning to brain disorders. Sample preparation was accomplished through a protein precipitation procedure using acetonitrile. Separation of teneligliptin and sitagliptin (IS) from endogenous components with high selectivity and sensitivity (0.5 ng/mL) was achieved within 4 min using Poroshell 120 EC-C18 column (100 × 3.0 mm, 2.7 μ). A gradient mobile phase consisting of 10 mM ammonium formate and acetonitrile was applied at a flow rate of 0.45 mL/min. Detection of target ions [M + H]+ at m/z 427.2274 for teneligliptin and m/z 408.1258 for IS was performed in selective ion mode using positive ion electrospray ionization high resolution accurate mass spectrometry. The linearity of the method was found to be in the range of 0.5–1000 ng/mL. The matrix effect was 88.7–94.5% for teneligliptin. Plasma samples were found to stable under different storage conditions. It was successfully applied to pharmacokinetic and plasma protein binding study of drug in rats. Results showed linear dose proportionality of pharmacokinetics at 0.1 and 1 mg/kg and relatively high protein binding of teneligliptin (85.46 ± 0.24 %) compared with other DPP-4 inhibitors.