DEGRADATION KINETICS OF THE ANTITUMOR DRUG NIMUSTINE (ACNU) IN AQUEOUS-SOLUTION

The degradation kinetics of the nitrosourea derivative nimustine has b een investigated over the H-0/pH region - 1 to 11 at 25-degrees-C. The stability tests were performed using a stability-indicating high-perf ormance liquid chromatographic assay. The first degradation product of nimustine is o-7-methylpyrimido[4,5-alpha]pyrimidine-2-(1H)one. Maxim um stability of nimustine is around pH 3. At higher and lower pH value s the degradation rate increases proportionally with [OH-] and [H+], r espectively. From the log k(obs)-pH plot a pK(a) value of 6.24 could b e derived. The influences of ionic strength and buffer ions were inves tigated at pH 5 and 9 but showed no effect on the degradation rate. Te mperature effects were studied at pH 1.0, 5.0 and 9.0. The degradation mechanism of nimustine is discussed.