Abstract:

HPLC was used to study the dynamic degradation of catalitaxol at different temperatures. Establishing the dynamic degradation model of catalitaxol in Endophyte FSN002, the effect of the temperature on the stability of catalitaxol was quantitatively analyzed. It was found that the thermal degradation of catalitaxol in Endophyte FSN002 was first-order reaction kinetics. The thermal degradation rate constant increased rapidly with increasing temperature, fitting the Arrhenius equation. The half-life of catalitaxol at 4℃ was 25 d and it was shortened to 6 d at 25 ℃, while it was only 14 h at 55℃. The model predicted that the half-life of catalitaxol would be only 3.7 h at 70℃. The rotary evaporation of catalitaxol from Endophyte FSN002 would cause substantial degradation and low yield, which was entirely consistent with the experimental verification.

Key words: pharmaceuticals, catalitaxol, degradation, instability, temperature, kinetic modeling

摘要：

用高效液相色谱检测不同温度下楸灵素降解的动态变化。建立楸灵素热降解动力学模型,定量分析温度对楸灵素稳定性的影响。实验发现楸灵素在发酵液中的热降解符合一级反应动力学,热降解速率常数随温度提高而快速上升,符合Arrhenius方程。4℃条件下楸灵素在发酵液中的半衰期长达25 d,25℃条件下则缩短为6 d,而55℃条件则进一步下降到14 h。模型预测楸灵素在70℃半衰期只有3.7 h,楸灵素发酵液旋转蒸发会造成大量降解,收率低下,与验证实验结果完全吻合。

关键词: 药物, 楸灵素, 降解, 不稳定性, 温度, 动力学模型