Determination of the Chemical Stability of Dapagliflozin by LC/DAD and MS/MS Methods.

Abstract

A simple and fast stability-indicating liquid chromatographic method with diode array detection (DAD) was developed and validated for the determination of dapagliflozin (DAPA) in bulk and tablets, in the presence of its major degradation products (DP). The drug was subjected to hydrolytic, oxidative, photolytic, thermal and humidity/thermal stress conditions, showing significant degradation under humidity/thermal with the formation of two DP, which were preliminarily identified by liquid chromatography with diode array detector coupled with electrospray ionization-tandem mass spectrometry (HPLC-DAD-ESI-MS/MS). Chromatographic separation of dapagliflozin and its DP was achieved with a core-shell RP-18 column, using acetonitrile and water as mobile phase in isocratic elution mode. The described method was linear over a range of 50-150μg/mL. For precision, the relative standard deviation (RSD) was <1.3%, the recovery was 99.64-100.11%, and the assay demonstrated adequate selectivity. The degradation kinetics of dapagliflozin was evaluated corresponding to first-order under thermal and humidity/thermal stress conditions. Dapagliflozin was well resolved from its drug products showing the power of stability-indicating of the method. The results showed that the proposed method was found to be suitable for routine analysis, quantitative determination and the stability study of dapagliflozin in pharmaceutical samples.