Degradation study of thiotepa in aqueous solutions

The degradation of N,N',N"-triethylenethiophosphoramide (thiotepa) in aqueo us solutions has been investigated over the pH range 1-14. Samples were ana lyzed using a high-performance liquid chromatographic system with UV detect ion. The degradation kinetics were studied as a function of pH, sodium chlo ride concentration and temperature. The degradation of thiotepa follows pse udo first order kinetics. The pH-log k(obs) profile shows that thiotepa is most stable in the pH range 7-11. At pH > 11 chloride has no influence on t he degradation rate. The degradation products were isolated and the structu res identified by mass spectrometry. Chloro adducts of thiotepa are generat ed 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. (C) 1999 Elsevier Science B.V . All rights reserved.