Dine T, Khalfi F, Gressier B, Luyckx M, Brunet C, Ballester L, Goudaliez F, Kablan J, Cazin M, Cazin J C
Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques, Lille, France.
J Pharm Biomed Anal. 1998 Nov;18(3):373-81. doi: 10.1016/s0731-7085(98)00096-x.
The stability and compatibility of fotemustine, a nitrosourea anticancer agent, in 5% dextrose solution with polyvinyl chloride (PVC) containers and administration sets were studied under different conditions of temperature and light. The drug was diluted to 0.8 and 2 mg ml(-1) in 100 or 250 ml 5% dextrose injection solutions for 1-h simulated infusions using PVC bags and administration sets with protection from light. After preparation in the PVC bags containing 5% dextrose, fotemustine was also prepared at the same concentrations and stored at 4 degrees C for 48 h and at room temperature (22 degrees C) or at sunray exposure ( > 30 degrees C) over 8 h with or without protection from light. The solution samples were removed immediately at various time points of simulated infusions and storage, and stored at -20 degrees C until analysis. The physical compatibility with PVC and chemical stability in solution of fotemustine were assessed by visual examination and by measuring the concentration of the drug in duplicate using a stability-indicating high-performance chromatographic assay. When admixed with a 5% dextrose solution, fotemustine 2 and 0.8 mg ml(-1) was compatible and stable over 1-h of simulated infusion using PVC bags through PVC administration sets with protection from light. On the other hand, in the same diluent, fotemustine was compatible and stable with PVC bags for at least 8 h at 22 degrees C with protection from light and for at least 48 h at 4 degrees C with protection from light. There were no pH variation, no visual change, no color change, no visible precipitation and no loss of the drug. Conversely, when the solutions were exposed to light (ambient or solar), the drug concentration decreased rapidly, leading to the production of a degradation product as shown by mass spectral analysis and a discoloration of the solutions. Finally, in all cases, no DEHP (di-2-ethylhexyl phthalate) was detected in the injection solution.
研究了亚硝基脲类抗癌药福莫司汀在不同温度和光照条件下，于含5%葡萄糖溶液的聚氯乙烯（PVC）容器及输液装置中的稳定性和相容性。将药物分别稀释至0.8和2mg/ml，置于100或250ml 5%葡萄糖注射液中，使用带避光保护的PVC袋和输液装置进行1小时模拟输注。在含5%葡萄糖的PVC袋中配制后，福莫司汀也以相同浓度配制，并在4℃避光保存48小时，在室温（22℃）或光照（>30℃）下暴露8小时，有无避光保护均可。在模拟输注和储存的不同时间点立即取出溶液样品，并在-20℃保存直至分析。通过目视检查以及使用稳定性指示高效液相色谱法重复测量药物浓度，评估福莫司汀与PVC的物理相容性及其在溶液中的化学稳定性。当与5%葡萄糖溶液混合时，2mg/ml和0.8mg/ml的福莫司汀在使用带避光保护的PVC袋通过PVC输液装置进行1小时模拟输注过程中是相容且稳定的。另一方面，在相同稀释剂中，福莫司汀在22℃避光条件下与PVC袋至少相容稳定8小时，在4℃避光条件下至少相容稳定48小时。无pH值变化、无目视变化、无颜色变化、无可见沉淀且无药物损失。相反，当溶液暴露于光照（环境光或太阳光）下时，药物浓度迅速下降，质谱分析显示产生了一种降解产物，溶液也出现变色。最后，在所有情况下，注射液中均未检测到邻苯二甲酸二（2-乙基己基）酯（DEHP）。
