Canagliflozin oxidation study using electrochemical flow cell and comparison with hydrogen peroxide oxidation
Abstract
By standards, the effect on oxidation of an active substance is tested using hydrogen peroxide solution at elevated temperature in a stress chamber for 1-7 days. An alternative way to study the effect of oxidation on an active substance is to use an electrochemical flow cell.
Solution with active substance flows at low flow rate into a small reactor, where the active substance is oxidized on working electrode surface. The electrolyte stream with the oxidized active substance is then directed to the sample collector.
Products of electrochemical oxidation are analyzed by high performance liquid chromatography with ultraviolet-visible spectrophotometry detection. Canagliflozin has been used because its main degradation pathway is oxidation.
The design of experiments approach was used to explore the experimental space and optimize experimental conditions of oxidation. The results of the oxidation study performed in the electrochemical flow cell were statistically compared with the results of a standard study using hydrogen peroxide solution.
The most suitable conditions for electrochemical oxidation were found. Electrochemical oxidation produced comparable amounts of impurities as chemical oxidation with hydrogen peroxide.