Kaijser G P, Beijnen J H, Bult A, Hogeboom M H, Underberg W J
Department of Pharmaceutical Analysis, Faculty of Pharmacy, Utrecht University, The Netherlands.
J Pharm Biomed Anal. 1991;9(10-12):1061-7. doi: 10.1016/0731-7085(91)80045-b.
The degradation kinetics of ifosfamide in aqueous solution have been investigated over the pH region 1-13 at 70 degrees C. A stability indicating high-performance liquid chromatographic assay with UV detection was used to separate degradation products from the parent compound. The degradation kinetics were studied as related to pH, buffer composition, ionic strength, temperature and drug concentration. A pH-rate profile at 70 degrees C, obtained from (pseudo) first-order kinetic plots, was constructed after corrections for buffer effects were made. The degradation reactions of ifosfamide were found to be largely independent of pH, although proton or hydroxyl catalysis occurs at extreme pH values. Ifosfamide shows maximum stability in the pH region 4-9, corresponding to a half-life of 20 h.
在70℃下,研究了异环磷酰胺在pH值为1至13的水溶液中的降解动力学。采用具有紫外检测的稳定性指示高效液相色谱法将降解产物与母体化合物分离。研究了降解动力学与pH值、缓冲液组成、离子强度、温度和药物浓度的关系。在对缓冲液效应进行校正后,根据(伪)一级动力学图构建了70℃下的pH-速率曲线。发现异环磷酰胺的降解反应在很大程度上与pH值无关,尽管在极端pH值下会发生质子或羟基催化。异环磷酰胺在pH值为4至9的区域表现出最大稳定性,相应半衰期为20小时。