Assessment of the stability of new chemotherapeutic selenium-kojic acid derivative using HPLC and MS analysis

ABSTRACT The stability of the new chemotherapeutic selenium kojic acid derivative, 5-benzyloxy-2-selenocyanatomethyl-4-pyranone (P763), was evaluated in simulated gastric and intestinal fluids as well as in human plasma at 37 o C ± 1. A stability-indicating HPLC procedure with C8 RP column and a mobile phase of acetonitrile/water (1:1) at a flow rate 1 ml/min was used. The eluted P763 compound and its degradation products were detected at 254 nm. The accelerated stability profiles were established. Kinetic studies under controlled experimental conditions have proved that P763 underwent fast hydrolysis in simulated intestinal fluid (phosphate buffer solution, pH 7.4), however the compound showed an appropriate stability at gastric acid solution (0.1M HCl solution) and in human plasma. The kinetics have indicated that the compound's degradation followed pseudo first-order reaction with relatively higher k deg and lower t 1/2 and t 90 values in simulated intestinal fluid compared to those in simulated gastric acid solution and plasma. The degradation of P763 compound at basic solution was confirmed by MS and MS/MS analysis, where the characteristic signals of the molecular (m/z 322) and fragment (m/z 91, 198) mass ions of compound disappeared. The obtained results suggest that the stability of P763 compound should be considered for future biopharmaceutical and biological studies