Stability of azacitidine in sterile water for injection.

BACKGROUND The product monograph for azacitidine states that once reconstituted, the drug may be held for only 30 min at room temperature or 8 h at 4°C. Standard doses result in wastage of a portion of each vial, and the cost of this wastage is significant, adding about $156 000 to annual drug expenditures at the authors' institution. OBJECTIVE To evaluate the stability of azacitidine after reconstitution. METHODS Vials of azacitidine were reconstituted with sterile water for injection. At the time of reconstitution, the temperature of the diluent was 4°C for samples to be stored at 4°C or -20°C and room temperature for samples to be stored at 23°C. Solutions of azacitidine (10 or 25 mg/mL) were stored in polypropylene syringes and glass vials at room temperature (23°C), 4°C, or -20°C. The concentration of azacitidine was determined by a validated, stability-indicating liquid chromatographic method in serial samples over 9.6 h at room temperature, over 4 days at 4°C, and over 23 days at -20°C. The recommended expiry date was determined on the basis of time to reach 90% of the initial concentration according to the fastest observed degradation rates (i.e., lower limit of 95% confidence interval). RESULTS Azacitidine degradation was very sensitive to temperature but not storage container (glass vial or polypropylene syringe). Reconstitution with cold sterile water reduced degradation. At 23°C, 15% of the initial concentration was lost after 9.6 h; at 4°C, 32% was lost after 4 days; and at -20°C, less than 5% was lost after 23 days. CONCLUSIONS More than 90% of the initial azacitidine concentration will be retained, with 97.5% confidence, if, during the life of the product, storage at 23°C does not exceed 2 h, storage at 4°C does not exceed 8 h, and storage at -20°C does not exceed 4 days. These expiry dates could substantially reduce wastage and cost where the time between doses does not exceed 4 days.