Physicochemical stability of pevonedistat at 50, 100 and 200 µg/mL diluted in 0.9% sodium chloride and at 10 mg/mL in partially used vials.

ABSTRACT

OBJECTIVES: Pevonedistat is a new cytotoxic used in association with azacitidine for the treatment of acute myeloid leukaemia and high-risk myelodysplastic syndromes. The manufacturer indicates an 18-hour stability after dilution in dextrose 5% or 0.9% sodium chloride (0.9% NaCl) at 2-8°C. No information is given for re-using vials of pevonedistat.Our objectives were to study the physico-chemical stability of 50 and 200 µg/mL pevonedistat diluted in 0.9% NaCl, in glass tubes, 100 µg/mL in 0.9% NaCl in polyolefin infusion bags, and 10 mg/mL partially used vials with a Spike. All preparations were stored at 2-8°C, protected from light. MATERIALS AND METHODS: Due to the limited quantity of pevonedistat available for this study, we prepared test solutions at 50 and 200 µg/mL in glass tubes in a small volume of 20 mL. Inorder to verify the absence of a sorption phenomenon of the molecule onto polyolefin, we prepared two infusion bags at 100 µg/mL. We tested concentrated solution at 10 mg/mL. At each analysis time, we tested three samples of each condition by high performance liquid chromatography (HPLC) coupled with a photodiode array detector. Physical stability was evaluated by a visual and sub-visual inspection. We measured pH at each analysis time. RESULTS: Diluted solutions at 50 and 200 µg/mL in tubes and at 100 mg/mL in infusion bags retained more than 95% of the initial concentration for 14 days, the concentrated solution at 10 mg/mL did so for 7 days. No physical changes were detected visually or sub-visually. We found that pH values remained stable. CONCLUSION: All diluted solutions remained physically and chemically stable for 14 days, the concentrated solution did so for 7 days. No interactions between the polyolefin bag and pevonedistat were demonstrated. This new data allows re-using the concentrated solution of pevonedistat in a commercial glass vial with a Spike, and storing a preparation in case of non-administration.