Acid Degradation Study of Dapagliflozin: Structural Characterization of Dapagliflozin and its Degradation Products Using Advanced Analytical Techniques and In Silico Toxicity Prediction

Abstract

The research investigates the stress degradation behavior of Dapagliflozin (DAP), a type‐2 diabetic treatment, following International Council for Harmonization Guidelines. It found that DAP is stable in thermal, photolytic, neutral, and alkaline hydrolysis conditions, but significant degradation was detected in acid hydrolysis. Two novel degradation products (DPs) were identified and isolated in acid degradation, providing the first documented structural characterization of all two DPs. The identification of DPs was achieved through the use of ultra‐high‐performance liquid chromatography–mass spectrometry, semi‐preparative high‐performance liquid chromatography, and nuclear magnetic resonance spectroscopy for structural characterization. In acid degradation, a total of two primary DPs, degradation products 1 and 2 (DP1 and DP2), were found and separated. It was not previously reported that the two DPs that were generated were all new. This is the first time that these two DPs’ full structural characterizations employing cutting‐edge analytical techniques have been recorded. In the current work, liquid chromatography mass spectroscopy and nuclear magnetic resonance spectroscopy were employed to get a specific confirmation of DP structures. In the further, degrading impurity with lower runtime will also be identified using the current method.