穿琥宁的水解动力学研究

Study on Degradation Kinetics of Potassium Dehydroandrographolidi Succinas

目的 研究穿琥宁溶液的水解动力学特征。方法 使用HPLC法测定穿琥宁水溶液在不同药物浓度，不同pH值的缓冲溶液，不同缓冲对溶液，不同离子强度，不同温度下的水解动力学参数。结果 穿琥宁水解反应符合一级动力学方程。随着pH值增加，穿琥宁降解速率明显增加，在碱性条件下不稳定；随着缓冲溶液浓度的增加，穿琥宁降解速率显著增加；不同的缓冲溶液对穿琥宁降解的催化作用不同；离子强度对穿琥宁降解无显著影响。由阿仑尼乌斯曲线可以看到，温度对穿琥宁的稳定性具有重要影响，穿琥宁在pH8、磷酸缓冲溶液、温度60～90℃下的活化能为95．68KJ／mol。结论 穿琥宁水解属于一级降解反应。降解速率与溶液pH值、缓冲液的浓度、缓冲液的种类及温度有关，溶液pH值对穿琥宁水解影响显著。

Objective To investigate the hydrolytic degradation of the kinetic characteristics of Potassium Dehydroandrographolidi Succinas （DAS-K） in aqueous solution. Methods The HPLC method was used to determine the degradation kinetic parameters of DAS-K aqueous solution at different initial concentration, different pH, different ionic strength, various temperatures and in different buffer solutions. Results DAS-K hydrolytic degradation followed first-order kinetics as measured by HPLC. From pH 8, the hydrolytic degradation rate of DAS-K markedly increased with pH. DAS-K was unstable in alkaline pH solution. The species of buffer solutions seem to have different impact on the catalytic process. The ionic strength did not have significant effect on the stability of the drug. According to the Arrhenius plot, the dependence of the decomposition on temperature was a determining factor, the activation energy was estimated to be 95.68 KJ/mol in phosphate buffer solution at pH 8 and temperature from 60 to 90 ~C. Conclusion It was found that the hydrolytic degradation of DAS-K complied with first-order kinetics. The rate of hydrolytic degradation of DAS-K depended on the pH of solution, the buffer concentration, the buffer species and the temperature. Especially, pH value was an important factor in determining the rate of the hydrolytic degradation of the drug.