title: Systematic study on the chemical stability of the prodrug antitumor agent carzelesin (U-80,244)
abstract: The chemical stability of the novel anticancer agent carzelesin in aqueous buffer/acetonitrile (1:1, v/v) mixtures has been investigated utilizing a stability-indicating reversed-phase high-performance liquid chromatographic assay. The degradation kinetics of carzelesin has been studied as a function of pH, buffer composition, ionic strength, and temperature. Degradation of carzelesin follows (pseudo-) first-order kinetics. A pH-rate profile, using rate constants extrapolated to zero buffer concentration, was constructed demonstrating that carzelesin is most stable in the pH region 1-4. The degradation rate of carzelesin was not significantly affected by buffer components and by the ionic strength. In addition to the formation of the degradation products U-76,073, U-76,074, and aniline in alkaline medium and in acetate buffer solution, another degradation product was formed in acetate buffer solution. In perchloric acid buffer solution (pH* < 3), U-76,073 and U-76,074 could not be detected as degradation products.
authors.affiliation: Department of Pharmacy, Slotervaart Hospital/Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: J D
authors.initials: JD
authors.lastname: Vries
authors.forename: W G
authors.initials: WG
authors.lastname: Doppenberg
authors.forename: R E
authors.initials: RE
authors.lastname: Henrar
authors.forename: A
authors.initials: A
authors.lastname: Bult
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001572:Benzofurans / Q000737:chemistry / Q000493:pharmacokinetics*; D000080890:Duocarmycins; D006207:Half-Life; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics*; D009994:Osmolar Concentration
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D000080890:Duocarmycins; D007211:Indoles; C076570:carzelesin