A NOVEL STABILITY-INDICATING RP-UPLC METHOD FOR THE QUANTIFICATION OF IMPURITIES AND A NEW QDa MASS DETECTOR COUPLED WITH LC-PDA FOR IDENTIFICATION OF MASS OF DEGRADATION PRODUCTS IN A FIXED DOSE COMBINATION OF EMPAGLIFLOZIN AND LANIGLIPTIN TABLETS USED A

Abstract

A new UPLC method was developed for identification and quantification of process related impurities and degradation products in a new fixed dose combination product of empagliflozin and linagliptin tablets, which is used to treat type-2 diabetes. Chromatographic separation was obtained using a new phenomenex Luna omega polar C18, 100x2.1mm, 1.6µ and a gradient programme consisting of Mobile phase A: 10mM Potassium dihydrogen orthophosphate pH-3.0 and Mobile phase B: acetonitrile and methanol (55:45%v/v). Degradation impurities were monitored at a common wavelength of 225nm. The run time was 40 minutes within this run time the five related compounds, all major degradation impurities of empagliflozin and linagliptin were eluted which reduces the analysis time and solvent consumption. The combined drugs as well as individual blends were subjected to hydrolysis (water, acid and base), oxidative, photolytic and thermal stress conditions. Mass of major unknown degradation products were determined by LC-PDA coupled with a new QDA mass detector. The protanated molecular ion peaks for linagliptin at M+H were DP1-514.19 in water, acid, base, oxidative, photolytic and thermal stress conditions. DP2-515.14 in acid and base hydrolysis. DP3-544.18 in acid hydrolysis. For empagliflozin DP4- 365.13 in base hydrolysis. DP5-487.16 and DP6-487.14 in peroxide hydrolysis. DP7-470.91, DP8-502.08, DP9-538.01, DP10-326.98 and DP11-293.02 in acid hydrolysis. The developed method was validated as per international conference on harmonization guidelines (ICH) with respect to specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision and robustness.