Chemical stability of azacitidine suspensions for injection after cold-chain reconstitution of powder and storage.

Purpose: The 72-hour chemical stability of refrigerated syringes of azacitidine suspension prepared via a cold-chain method is investigated.

Methods: Three 25-mg/mL azacitidine suspensions were prepared from different lots of powdered drug. The suspensions were stored in 2-mL polypropylene syringes at 2-8 °C and protected from light. The concentrations of azacitidine and the mean area under the concentration-time curve (AUC) values for its degradation products were determined after 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours using high-performance liquid chromatography with ultraviolet detection.

Results: The degradation process was slow during the first 48 hours and then accelerated. During the first 48 hours of storage, 4.23% of the azacitidine was lost relative to the mean concentration measured at time zero, which complied with International Conference on Harmonisation (ICH) guidance specifying a maximum change of 5% from the initial measured value. Two degradation products were present immediately after syringe preparation; N-formylribosylguanylurea formed rapidly (as indicated by a 35.62% increase from the baseline AUC in the first 12 hours), whereas ribosylguanylurea formation occurred more slowly (a 7.69% mean increase from the baseline AUC at 12 hours) but then rapidly accelerated. The study results indicate that properly prepared azacitidine syringes for injection can be administered up to two days later while maintaining conformance with ICH stability standards.

Conclusion: Azacitidine 25-mg/mL suspensions reconstituted with refrigerated water (2-8 °C) and stored in propylene syringes were chemically stable during the first 48 hours when stored protected from light at 2-8 °C.