Objectives:

Using the RP-HPLC method, this work investigates the degradation behavior of canagliflozin and its commercial formulation under ICH-recommended stress conditions. It also validates the suggested method and analyzes degraded samples’ solution state using LC-MS/MS.

Materials and Methods:

The solution-state degradation study of canagliflozin in tablet dosage form was performed using the Shimadzu-HPLC series 1100. The acetonitrile (50:50) v/v mobile phase, ammonium acetate buffer pH 4.5 and an ACE BDS C18 column (150×2.5 mm, 4.6 mm) were utilized in the analysis. The wavelength chosen for the study was 291 nm, at which the drug displayed a strong peak and methanol was employed as diluent. An Agilent 1110-LC system was connected to a Shimadzu LC-MS/MS-8040 outfitted with a PDA-SPD M20A and an Electrospray Ionization (ESI) source interface for LC-MS analysis. Canagliflozin was exposed for 180 min at 50ºC in solution state degradation experiments using acidic, basic, neutral and peroxide conditions.

Results:

HPLC was used to detect the degradation products and HPLC-Mass Spectroscopy (LC/ MS/MS) was used to characterize them. Major peaks at 293.0, 281.70, 224.90, 221.50, 180.90, 145.90 and 104.90 were visible in the LC-MS data. It was found that the canagliflozin formulation which was marketed was labile under stress conditions which included neutral, oxidative, alkaline and acidic.

Conclusion:

The deteriorated samples were analyzed using the LC-MS/MS technique and potential structures were allocated in accordance with the drug’s known reactivity.

Keywords: Canagliflozin, Degradation, Kinetics, LC-MS/MS, Stability.