热毒宁注射液中绿原酸的降解动力学研究

目的: 研究热毒宁注射液中绿原酸(chlorogenic acid,CHA)在不同pH和温度条件下降解反应的动力学特征。 方法: 采用高效液相色谱法(HPLC)考察不同pH和温度下绿原酸对照品水溶液及热毒宁注射液中绿原酸的含量变化,利用化学反应动力学的方法计算绿原酸在不同环境下的降解反应动力学参数,用阿仑尼乌斯公式预测其有效期(t_0.9)、半衰期(t_0.5)和活化能(energy of activation,Ea)。 结果: 绿原酸在不同pH和温度下的降解反应均遵循一级动力学规律,在pH7水溶液中绿原酸的t_0.9=22 d、t_0.5=104 d、Ea=90.89 kJ·mol^-1;在热毒宁注射液中绿原酸的t_0.9=31 d、t_0.5=203 d、Ea=140.49 kJ·mol^-1。 结论: 绿原酸在水溶液及热毒宁注射液中均在酸性、低温条件下较稳定。同样条件下,绿原酸在热毒宁注射液中的稳定性都要高于绿原酸水溶液。可根据绿原酸降解动力学模型,用于热毒宁注射液有效性和稳定性的评价。

Objective: To investigate the degradation kinetic characteristics of chlorogenic acid(CHA) in reduning injection under different pH and temperature conditions. Methods: HPLC was employed for the study;the concentration changes of CHA in aqueous solution and reduning injection under different pH and temperature conditions were determined.Based on the chemical reaction kinetic,the parameters of degradation kinetics were calculated.The activation energy and shelf life were evaluated with Arrhenius equation. Results: Our results indicated that thermal degradation kinetic model of CHA in aqueous solution and reduning injection was a first-order degradation kinetic process.The period of validity (t_0.9) were 22 and 31 days;the half - life period (t_0.5) were 104 and 203 days under pH7 in aqueous solution and reduning injection.The energy of activation (Ea) was 90.89 kJ·mol^-1in aqueous solution and 140.49 kJ·mol^-1 in reduning injection. Conclusions: CHA is more stable in acidic and low temperature conditions both in aqueous solution and reduning injection.Under the same condition,CHA in reduning injection was more stable than in aqueous solution.The kinetic profile can be used for the evaluation of effectiveness and stability of reduning injection.