Comparative stability of kojic acid and its dipalmitate salt under oxidative stress conditions

Abstract

Introduction: Using Kojic Acid (KA) and its Di-Palmitate derivative (KADP), has showed a better efficacy and less adverse effects in topical skin anti-hyperpigmentation products. It is assumed that KADP is more stable. Aim: Comparative stability of kojic acid and its dipalmitate salt under oxidative stress conditions Method: A HPLC UV method with a C18 column was used. The methods for the two drugs were separately validated. The aqueous phase contained phosphate buffer and methanol (99:1) for KA and the organic lipophilic phase was composed of THF 35%, ACN30%, methanol 29% and a small amount of water for KADP. Oxidative stress was applied to both drugs separately and at different time intervals. To stop the reaction at the end of the stress، ice was used to reduce the temperature and methanol was added. Finally, the stress calculations were performed based on the validation results and the kinetics of the degradation were computed red for each drug. Results: The linear range for KA was (2-8 µg/ml) and (4-16µg/ml) for KADP. LOD and LOQ for KA were 0.086 and 0.28 µg/ml, and for KADP 1 and 3 µg/ml. The superior degradation model based on MPE mean was first degree for both drugs. Discussion: contrary to previous assumptions KA degraded in 6 to 48 hours while KADP was degraded in 5 to 90 minutes, indicating KADP as a more liable molecule in oxidative conditions. The superior degradation model was performed by calculating MPE mean, which was the first degree for both drugs indicating the dependency of the reaction rate on the initial concentration of the reactive substance. Finally KA is more stable in oxidative conditions than its palmitate ester.