KINETIC-STUDIES OF MELPHALAN THERMODEGRADATION BY HPLC

The kinetics of degradation of the antineoplastic alkylating agent, Melphalan, have been studied in the temperature range from 30-degrees-C to 55-degrees-C in different media conditions such as water, MEM Alpha, MEM Alpha + 10% fetal bovine serum and in PBS containing varying amounts of bovine serum albumin. The analysis was performed in 3 min by direct quantitation of Melphalan with a HPLC system equipped with a 3-mu-m C18 column and detected by a UV spectrophotometer at 256 nm. The degradation of Melphalan was faster in water and MEM Alpha (with or without fetal bovine serum) than in PBS as demonstrated by rate constants for the decay and half-life constants. The rate of Melphalan degradation increased with increasing temperature from 30-degrees-C to 55-degrees-C. Melphalan degradation followed first order decay kinetics and gave a linear relationship in agreement with the Arrhenius theory for all the incubation media studied. The activation energies for melphalan degradation in the different media conditions ranged from 88 to 91 kJ M-1.