Study on degradation kinetics of epalrestat in aqueous solutions and characterization of its major degradation products under stress degradation conditions by UHPLC-PDA-MS/MS / 药物分析学报

ABSTRACT

Drug stability is closely related to drug safety and needs to be considered in the process of drug production, package and storage. To investigate the stability of epalrestat, a carboxylic acid derivative, a reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed in this study and applied to analyzing the degradation kinetics of epalrestat in aqueous solutions in various conditions, such as dif-ferent pH, temperatures, ionic strengths, oxidation and irradiation. The calibration curve was A=1.6 × 105C–1.3 × 103 (r=0.999) with the liner range of 0.5–24 μg/mL, the intra-day and inter-day precision was less than 2.0%, as was the repeatibility. The average accuracy for different concentrations was more than 98.5%, indicating that perfect recoveries were achieved. Degradation kinetic parameters such as degradation rate constants (k), activation energy (Ea) and shelf life (t0.9) under different conditions were calculated and discussed. The results indicated that the degradation behavior of epalrestat was pH-dependent and the stability of epalrestat decreased with the rised irradiation and ionic strength;however, it was more stable in neutral and alkaline conditions as well as lower temperatures. The results showed that the degradation kinetics of epalrestat followed first-order reaction kinetics. Furthermore, the degradation products of epalrestat under stress conditions were identified by UHPLC-PDA-MS/MS, with seven degradation products being detected and four of them being tentatively identified.