Chemical stability of ecomustine, a new antitumor agent in aqueous and biological media as assessed by high-performance liquid chromatography

Abstract

Ecomustine, or CY233 (NSC-609224), is a new water-soluble nitrosoureido sugar derived from acosamine. A high-performance liquid chromatographic assay (HPLC) developed to quantify the unchanged drug in aqueous solutions and biological specimens enabled us to study the chemical stability as a function of pH, light, and temperature. In buffered aqueous solutions, the kinetics of degradation of CY233 is a first-order process. The log k-pH profile demonstrated hydroxide ion-catalyzed solvolysis. The drug is most stable at pH 4, more stable than some other nitrosoureas in 5% glucose (t1/2, 62-67 h) and in 0.9% isotonic saline (t1/2, 25-37 h) solutions. Based on these findings, blood samples should be collected in cold tubes (4 degrees C) containing citrate buffer (pH 4) and all manipulations should be protected from heat and light.