Physicochemical Stability of Reconstituted Decitabine (Dacogen®) Solutions and Ready-to-Administer Infusion Bags when Stored Refrigerated or Frozen

Abstract

AbstractBackgroundProfound knowledge about the physicochemical stability is necessary in order to determine the “beyond-use-dates” of ready-to-administer preparations after reconstitution and dilution. This is especially true for unstable azanucleoside drugs like decitabine. The aim of this study was to determine the physicochemical stability of decitabine after reconstitution and dilution of DacogenMethodsTo determine the stability of frozen DacogenTo determine the stability of reconstituted DacogenDiluted DacogenDecitabine concentrations were determined at 0, 5, 8, 12, 24 and 48 hours after preparation. The pH-values were determined at 0, 8, 24 and 48 hours. Each sample was assayed by a validated stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) assay with photodiode array detection.ResultsWhen test solutions of reconstituted DacogenIn reconstituted test solutions in glass vials and in diluted test solutions in infusion bags stored under refrigeration decitabine concentrations remained above 90 % of the initial concentration for 12 hours and 24 hours, respectively. Several peaks of degradation products were observed which explicitly increased over time.In all test solutions the pH-values amounted to pH 7 and remained unchanged. No particulate matter and no colour changes were observed over the test period.ConclusionsReconstituted decitabine solution (Dacogen