Ezquer-Garin Carlos, Ferriols-Lisart Rafael, Alós-Almiñana Manuel
Institute for Health Research (INCLIVA), Clinical University Hospital of Valencia, Spain.
Department of Pharmacy, University of Valencia, Valencia, Spain.
Biomed Chromatogr. 2019 Jul;33(7):e4529. doi: 10.1002/bmc.4529. Epub 2019 Mar 24.
Stability studies are necessary in healthcare settings as they facilitate fast, cost-effective and efficient work related to batch manufacturing and availability of supplies. We studied the stability of 1-10 mg/mL mycophenolate mofetil (MMF) in polypropylene 5% dextrose infusion bags prepared from Cellcept and with a generic brand name (Micofenolato de Mofetilo Accord) at different storage temperatures. To ensure chemical compatibility during preparation, we also tested MMF sorption to the Equashield closed-system drug transfer device used in this step. For this, a validated stability-indicating high-performance liquid chromatography method was developed for the quantification and identification of MMF in the infusion bags. The analytical selectivity of the assay was determined by subjecting an MMF sample to extreme values of pH, oxidative stress and heat conditions to force degradation. Protected from light, 1-10 mg/mL MMF in infusion polypropylene bags prepared from reconstituted Cellcept 500 mg or Accord 500 mg in 5% dextrose was stable for at least 35 days when stored at 2-8°C or between -15 and -25°C, and for 14 days when stored at 25°C. MMF loss owing to chemical sorption to the Equashield closed-system drug transfer device set was negligible.
稳定性研究在医疗环境中是必要的，因为它们有助于与批量生产和供应可用性相关的快速、经济高效的工作。我们研究了1-10毫克/毫升的霉酚酸酯（MMF）在由骁悉制备的、具有通用品牌名（麦考酚钠依诺）的聚丙烯5%葡萄糖输液袋中，在不同储存温度下的稳定性。为确保制备过程中的化学相容性，我们还测试了MMF对该步骤中使用的Equashield封闭系统药物转移装置的吸附情况。为此，开发了一种经过验证的稳定性指示高效液相色谱法，用于定量和鉴定输液袋中的MMF。通过使MMF样品经受pH值、氧化应激和热条件的极端值以促使其降解，来确定该分析方法的选择性。在避光条件下，由500毫克骁悉或500毫克依诺在5%葡萄糖中复溶后制备的输液聚丙烯袋中的1-10毫克/毫升MMF，在2-8°C或-15至-25°C储存时至少稳定35天，在25°C储存时稳定14天。MMF因化学吸附到Equashield封闭系统药物转移装置组上的损失可忽略不计。
