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 different 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 (t_0.9) 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.

药物稳定性与药物安全性密切相关，需要在药物生产，包装和储存过程中加以考虑。为了研究依帕司他的稳定性，本研究开发了一种羧酸衍生物，反相高效液相色谱（RP-HPLC）方法，并用于分析依帕司他在各种条件下的水溶液中的降解动力学。不同的pH，温度，离子强度，氧化和辐照。校准曲线为A  = 1.6×10 ⁵ C –1.3×10 ³（r = 0.999），且线性范围为0.5–24μg/ mL，日内和日间精度小于2.0％，重复性也小于2.0％。不同浓度的平均准确度超过98.5％，表明可以实现完美的回收率。降解动力学参数，例如降解速率常数（k），活化能（Ea）和保质期（t _0.9））在不同条件下的计算和讨论。结果表明，依帕司他的降解行为与pH有关，依帕司他的稳定性随辐照度和离子强度的增加而降低。但是，它在中性和碱性条件以及较低的温度下更稳定。结果表明，依帕司他的降解动力学遵循一级反应动力学。此外，通过UHPLC-PDA-MS / MS鉴定了依帕瑞司他在应激条件下的降解产物，共检测到七个降解产物，并初步鉴定了其中四个。