PP-009 Stability of intraveous injection of decitabine stored in polyethylene syringes

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Abstract

Background

Decitabine is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) de novo or secondary, according to the classification of the WHO, who are not candidates for conventional induction chemotherapy. There is a general recommendation about the maximum refrigerated (2–8°C) storage time for decitabine of 3 hours, but studies designed to explore stability beyond this period have not been conducted to date.

Purpose

To evaluate the physical and chemical stability of decitabine stored in polyethylene syringes over a 24 hour period using proton nuclear magnetic resonance (1H-NMR) spectroscopy.

Material and methods

Commercial solutions of decitabine (Dacogen) 5 mg/mL (50 mg in 10 mL of sterile water for injection) were packaged in polyethylene syringes. The syringe was stored in a refrigerator at 4°C±2°C for 24 hours in a digitalised temperature controlled chamber. The following physical parameters were monitored: turbidity and colour. Chemical stability was assessed by means of 1H-NMR spectroscopy. The 1H-NMR spectrum of a reference molecule was acquired. Spectroscopic signals were interpreted and assigned to the chemical structure of decitabine, and then consecutive spectra were acquired every hour during the 24 hour period. Signals obtained in these experiments were compared with those of the reference compound. All spectra were acquired using a Bruker Avance DRX 300 MHz spectrometer equipped with a 5 mm single axis z gradient quattro nucleus probe (Bruker Biospin GmbH, Rheinstetten, Germany).

Results

Physical parameters monitored remained unchanged over the 24 hour period. During 7 hours, the chemical structure of the molecule was maintained unaltered, as demonstrated by 1H-NMR spectra identical to those of the reference compound. However, several signals corresponding to byproducts appeared in the sample stored at 4°C after 7 hours, proving that decitabine had suffered a degradation pathway.

Conclusion

Decitabine preserved its physical and chemical properties when stored packaged in polyethylene syringes for up to 7 hours at 4°C±2°C. This study comes into conflict with the information data sheet provided with decitabine, which recommends a maximum time of refrigerated (2–8°C) storage of 3 hours.

References and/or acknowledgements

University of Almería.

References and/or acknowledgements

No conflict of interest

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