van Maanen M J, Brandt A C, Damen J M, Beijnen J H
University of Utrecht, Department of Pharmaceutical Analysis, Sorbonnelaan 16, 3584 CA, Utrecht, The Netherlands.
Int J Pharm. 1999 Mar 1;179(1):55-64. doi: 10.1016/s0378-5173(98)00384-6.
The degradation of N,N',N"-triethylenethiophosphoramide (thiotepa) in aqueous solutions has been investigated over the pH range 1-14. Samples were analyzed using a high-performance liquid chromatographic system with UV detection. The degradation kinetics were studied as a function of pH, sodium chloride concentration and temperature. The degradation of thiotepa follows pseudo first order kinetics. The pH-log kobs profile shows that thiotepa is most stable in the pH range 7-11. At pH?11 chloride has no influence on the degradation rate. The degradation products were isolated and the structures identified by mass spectrometry. Chloro adducts of thiotepa are generated in the presence of sodium chloride and in acidic medium. In the pH range 7-11 only the mono-chloro adduct of thiotepa could be found. No detectable degradation products were formed at pH?11.
在pH值为1至14的范围内，对水溶液中N,N',N"-三亚乙基硫代磷酰胺（噻替派）的降解情况进行了研究。使用配备紫外检测的高效液相色谱系统对样品进行分析。研究了降解动力学与pH值、氯化钠浓度和温度的关系。噻替派的降解遵循准一级动力学。pH-log kobs曲线表明，噻替派在pH值7至11的范围内最稳定。在pH值≤11时，氯化物对降解速率没有影响。分离出降解产物，并通过质谱法鉴定其结构。在氯化钠存在和酸性介质中会生成噻替派的氯加合物。在pH值7至11的范围内，仅能检测到噻替派的单氯加合物。在pH值≤11时未形成可检测到的降解产物。
