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.