Doncheva Ralitsa, D'Huart Elise, Sobalak Nathalie, Vigneron Jean, Demoré Béatrice
Pharmacy, CHU Nancy Pharmacy, Vandoeuvre lès Nancy, France
Non-profit Association, Infostab, Heillecourt, France.
Eur J Hosp Pharm. 2025 Aug 21;32(5):479-484. doi: 10.1136/ejhpharm-2023-003884.
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.
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.
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.
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.
培沃替尼是一种新型细胞毒性药物，与阿扎胞苷联合用于治疗急性髓系白血病和高危骨髓增生异常综合征。制造商表明，在2-8°C条件下，在5 %葡萄糖或0.9 %氯化钠（0.9 % NaCl）中稀释后，其稳定性为18小时。未提供关于重复使用培沃替尼小瓶的信息。我们的目的是研究在玻璃管中用0.9 % NaCl稀释至50和200 μg/mL的培沃替尼、在聚烯烃输液袋中用0.9 % NaCl稀释至100 μg/mL的培沃替尼以及带有穿刺装置的部分使用过的10 mg/mL小瓶的物理化学稳定性。所有制剂均储存于2-8°C，避光保存。
由于本研究可用的培沃替尼数量有限，我们在玻璃管中以小体积20 mL制备了浓度为50和200 μg/mL的测试溶液。为了验证该分子在聚烯烃上不存在吸附现象，我们制备了两个浓度为100 μg/mL的输液袋。我们测试了浓度为10 mg/mL的浓缩溶液。在每个分析时间点，我们通过配备光电二极管阵列检测器的高效液相色谱（HPLC）对每种条件下的三个样品进行测试。通过目视和亚目视检查评估物理稳定性。我们在每个分析时间点测量pH值。
在玻璃管中稀释至50和200 μg/mL以及在输液袋中稀释至100 mg/mL的溶液在14天内保持初始浓度的95 %以上，浓度为10 mg/mL的浓缩溶液在7天内保持如此。在目视或亚目视检查中未检测到物理变化。我们发现pH值保持稳定。
所有稀释溶液在物理和化学上均保持稳定14天，浓缩溶液保持稳定7天。未证明聚烯烃袋与培沃替尼之间存在相互作用。这些新数据允许在带有穿刺装置的商用玻璃小瓶中重复使用培沃替尼的浓缩溶液，并在未给药时储存制剂。
