Degradation study of thiotepa in aqueous solutions.
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.
University of Utrecht, Department of Pharmaceutical Analysis, Sorbonnelaan 16, 3584 CA, Utrecht, The Netherlands. M.J.vanMaanen@far.ruu.nl
M J
MJ
van Maanen
A C
AC
Brandt
J M
JM
Damen
J H
JH
Beijnen
D000465:Algorithms; D000477:Alkylating Agents / Q000737:chemistry*; D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D017022:Flow Injection Analysis; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D013058:Mass Spectrometry; D012965:Sodium Chloride / Q000032:analysis; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D013852:Thiotepa / Q000737:chemistry*
D000477:Alkylating Agents; D002021:Buffers; D012996:Solutions; D012965:Sodium Chloride; D013852:Thiotepa