Identification, Isolation and Structural Elucidation of New Inner Salt Impurity in Vildagliptin and Metformin Tablet by Using Supercritical Fluid Chromatography, NMR, HRMS

Abstract

Vildagliptin is an orally active antihyperglycemic agent used for the treatment of type 2 diabetes mellitus in adults as monotherapy either alone or in combination with metformin. The presence of impurities in drug substances or drug products could be toxic and unsafe (injurious) to the user, and it should be ensured that drugs must be free of or controlled from any impurities to the specified level as per International Council for Harmonization guidelines before that reaches the user. That is the reason why work on identification, isolation, and characterization of impurities in drug substances and drug products is very important towards ensuring drug safety and efficacy. Further, product-related impurity isolation and characterization is an important aspect of pharmaceutical processes. The aim of the work is to identify a new impurity which was detected in vildagliptin and metformin tablets under stability storage conditions by using high-performance liquid chromatography (HPLC). The new impurity was isolated and characterized by using comprehensive analysis of HPLC, flash chromatography, supercritical fluid chromatography, Fourier transform infrared spectroscopy, high-resolution mass spectrometry, 1D-NMR [¹H and ¹³C], and 2D-NMR (¹H-¹H correlated spectroscopy, total correlated spectroscopy, ¹H-¹³C heteronuclear single quantum coherence spectroscopy, ¹H-¹³C and ¹H-¹⁵N heteronuclear multiple bond coherence spectroscopy) spectroscopic data.