Degradation of dacarbazine in aqueous solution.
The effects of initial concentration (0.05-5.0 mg ml-1, 2.5 x 10(-4)-0.025 M) (pH 1-13), buffer concentration (0.01-0.075 M), light, antioxidants and co-solvents on the degradation of dacarbazine in aqueous solution were investigated at 37 degrees C. Liquid chromatography was used to monitor the degradation of dacarbazine as well as the appearance of degradation products. The kinetics of hydrolysis of dacarbazine in the dark were pseudo first-order and independent of the initial concentration of the drug. The degradation of dacarbazine was accelerated by light and at low concentration proceeded by pseudo zero-order kinetics. The pH-rate profiles showed that both the photolytic and the hydrolytic reactions were dependent on the ionization state of the molecule. The main degradation product of both hydrolysis and photolysis was detected by liquid chromatography and confirmed by mass spectrometry to be 2-azahypoxanthine.
Shetty
B V
BV
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66046.
Schowen
R L
RL
Slavik
M
M
Riley
C M
CM
D002021:Buffers; D002853:Chromatography, Liquid; D003606:Dacarbazine / Q000032:analysis*; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007202:Indicators and Reagents; D007700:Kinetics; D013058:Mass Spectrometry; D010777:Photochemistry; D012996:Solutions
D002021:Buffers; D007202:Indicators and Reagents; D012996:Solutions; D003606:Dacarbazine