SYSTEMATIC STUDY ON THE CHEMICAL-STABILITY OF THE PRODRUG ANTITUMOR AGENT CARZELESIN (U-80,244)

The chemical stability of the novel anticancer agent carzelesin in aqu eous buffer/acetonitrile (1:1, v/v) mixtures has been investigated uti lizing a stability-indicating reversed-phase high-performance liquid c hromatographic assay. The degradation kinetics of carzelesin has been studied as a function of pH, buffer composition, ionic strength, and t emperature. Degradation of carzelesin follows (pseudo-) first-order ki netics. A pH-rate profile, using rate constants extrapolated to zero b uffer concentration, was constructed demonstrating that carzelesin is most stable in the pH region 1-4. The degradation rate of carzelesin w as not significantly affected by buffer components and by the ionic st rength. In addition to the formation of the degradation products U-76, 073, U-76,074, and aniline in alkaline medium and in acetate buffer so lution, another degradation product was formed in acetate buffer solut ion. In perchloric acid buffer solution (pH < 3), U-76,073 and U-76,0 74 could not be detected as degradation products.