Stabilization and preformulation of anticancer drug--SarCNU.

The stability of SarCNU (NSC364432), 1-(2-chloroethyl)-3-sarcosinamide-1-nitrosourea in several pharmaceutically acceptable solvents was investigated by high pressure liquid chromatography (HPLC). The influences of light, ionic strength, pH, buffer concentration, and the following excipients: benzyl alcohol, ascorbic acid, sodium bisulfite, and disodium EDTA were studied at room temperature. The stability of the drug was also determined in water, EtOH, PG, Capmul PG, DMSO, and in different combinations of these cosolvents at four different temperatures. The degradation of the drug, which is catalyzed not only by general but also by specific acid and base, follows first order kinetics. Antioxidants, EDTA, and light have no effect on the degradation rate, suggesting oxidation is not a major degradation pathway. The t(90) in pure cosolvent is 25-50 times higher than that in water or semi-aqueous vehicles. Neat EtOH can be used to store the drug in a nonaqueous concentrate that is diluted with aqueous solvent prior to injection.