Pharmacy, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-lès-Nancy, France.
Pharmacy, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-lès-Nancy, France
Eur J Hosp Pharm. 2023 Mar;30(e1):e29-e34. doi: 10.1136/ejhpharm-2021-002935. Epub 2021 Aug 18.
Cefiderocol is a new siderophore time-dependent antibiotic of last resort. The manufacturer reports a stability of 6 hours for the infusion solution diluted in normal saline (NS) or dextrose 5% in water (D5W) for a concentration between 7.5 and 20 mg/mL. Optimising its effectiveness by continuous infusion is crucial. The aim of this work was to study the physicochemical stability of cefiderocol diluted in NS or D5W in polypropylene syringes for 48 hours at a concentration of 62.5 mg/mL stored at room temperature, protected or not from light.
Three preparations for each condition were performed. At each time of the analysis, one sample for each preparation was analysed in triplicate by a validated high performance liquid chromatography method coupled to a photodiode array detector at 260 nm. Particle contamination, absorbance measurement, visual inspection and pH measurement were assessed. The limit of stability was set at 90% of the initial concentration, without physical modification.
The linearity was validated with an R² of 0.9999. The coefficients of variation for repeatability and intermediate precision were less than 2%. In NS and D5W, cefiderocol retained more than 90% of the initial concentration after 12 hours in syringes, exposed or not to light. Two degradation products (nos 2 and 11, observed during forced degradation) were detected during the stability study. The absorbance at 410 nm increased progressively, regardless of the storage conditions. The particulate contamination test met the specifications of the container. pH values were all between 5.22 and 5.32. No visual changes were detected.
In polypropylene syringes, cefiderocol 62.5 mg/mL (3 g in 48 mL) diluted in NS or D5W was stable for 12 hours at room temperature. These new data allow the use of cefiderocol in continuous infusion.
头孢他啶罗是一种新型的铁载体时间依赖性抗生素，属于最后手段。制造商报告称，在浓度为 7.5 至 20mg/mL 之间，稀释在生理盐水（NS）或 5%葡萄糖水中（D5W）的输液溶液在室温下可稳定 6 小时。通过连续输注来优化其效果至关重要。本研究的目的是研究在室温下，浓度为 62.5mg/mL 的头孢他啶罗在聚丙烯注射器中分别用 NS 或 D5W 稀释，在 48 小时内的物理化学稳定性，是否避光。
每种条件下均进行 3 次制备。在分析的每个时间点，从每个制备的 1 个样本中进行 3 次重复分析，使用经验证的高效液相色谱法与 260nm 处的光电二极管阵列检测器相结合。评估了粒子污染、吸光度测量、目视检查和 pH 值测量。稳定性的下限设定为初始浓度的 90%，没有物理变化。
线性验证的 R²为 0.9999。重复性和中间精密度的变异系数小于 2%。在 NS 和 D5W 中，头孢他啶罗在注射器中暴露或不暴露于光线下，在 12 小时后仍保留初始浓度的 90%以上。在稳定性研究中检测到 2 种降解产物（在强制降解过程中观察到的 2 号和 11 号）。无论储存条件如何，410nm 处的吸光度都在逐渐增加。颗粒污染测试符合容器的规格。pH 值均在 5.22 至 5.32 之间。未检测到肉眼可见的变化。
在聚丙烯注射器中，浓度为 62.5mg/mL（3g 在 48mL 中）的头孢他啶罗用 NS 或 D5W 稀释，在室温下可稳定 12 小时。这些新数据允许连续输注使用头孢他啶罗。
