Reactions of 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in aqueous solution

Abstract

Products formed from the reaction of 2 chloroethylnitrosoureas [antineoplastic drugs] in neutral aqueous solution were identified and quantified. Mixture components recovered after a 1 h incubation period accounted for 75-85% of the starting nitrosourea. Approximately 65-85% of the reaction products were formed by an initial cleavage of the nitrosourea to the proposed intermediates 2-chloroethyl azohydroxide and an isocyanate and by subsequent hydrolytic reactions. A minor pathway, 5-10% of products, involves denitrosation of the nitrosourea with oxazoline formation. Stable isotope labeling and mass spectrometry were used to determine the reaction sequence and product origins. Reaction product identification was made using high performance liquid chromatography isolation and comparison with synthetic material.