Simar J, Godet M, Hecq J-D, Closset M, Gillet P, Langhendries C, Bihin B, Jamart J, Galanti L
Medical Laboratory, CHU UCL Namur, 1, avenue Therasse, 5530 Yvoir, Belgium.
Medical Laboratory, CHU UCL Namur, 1, avenue Therasse, 5530 Yvoir, Belgium; Drug Stability Research Group, CHU UCL Namur, 1, avenue Therasse, 5530 Yvoir, Belgium.
Ann Pharm Fr. 2017 Jan;75(1):30-39. doi: 10.1016/j.pharma.2016.08.001. Epub 2016 Sep 12.
The aim of the study was to investigate the long-term stability of dexamethasone 10mg associated with alizapride 100mg or ondansetron 8mg in 100mL of 0.9% sodium chloride solution stored at 5±3°C.
Solutions of 0.9% sodium chloride 100mL in polyolefin bags (n=5) containing approximately dexamethasone (DEX) 10mg associated with alizapride (ALI) 100mg or ondansetron (OND) 8mg were prepared under aseptic conditions and stored about 30 days at 5±3°C. ALI, DEX and OND concentrations were measured by high-performance liquid chromatography (HPLC). Optic density measurement at different wavelengths, pH measurement and optic microscope observations were performed periodically during the storage. A forced degradation test with HCL 5M and NaOH 5M before and after heating at 100°C was also performed. Solutions were considered stable if the 95% one-sided lower confidence limit of the concentration remains superior to 90% of the initial concentration or 95% of the initial concentration when any signs of physical instability exist as recently recommend.
The calibration was linear over the following range from 20 to 1.25mg/100mL for DEX, from 200 to 12.5mg/100mL for ALI and from 20 to 1.25mg/100mL for OND with a calculated correlation coefficient (r) of 0.998, 0.999 and 0.999, respectively. The inter- and intra-assay precision was below 10% for both mixtures. All formulations were physically stable during the storage. The lower confidence limit of the concentration for these solutions remains superior to 90% of the initial concentration at this date as recommended by the Food and Drug Administration (FDA) until 30 days.
The HPLC method is specific and reproducible and can easily be adopted for monitoring the quality control in the production of DEX-ALI and DEX-OND bags. Solutions of DEX-ALI and DEX-OND were physically and chemically stable for 30 days in polyolefin bags stored at 5±3°C and could therefore be prepared in advance.
本研究的目的是调查在5±3°C下储存的100mL 0.9%氯化钠溶液中，10mg地塞米松与100mg阿立必利或8mg昂丹司琼混合后的长期稳定性。
在无菌条件下，制备5个含有约10mg地塞米松（DEX）与100mg阿立必利（ALI）或8mg昂丹司琼（OND）的100mL聚烯烃袋包装的0.9%氯化钠溶液，并在5±3°C下储存约30天。通过高效液相色谱法（HPLC）测定ALI、DEX和OND的浓度。在储存期间定期进行不同波长下的光密度测量、pH测量和光学显微镜观察。在100°C加热前后，还用5M盐酸和5M氢氧化钠进行了强制降解试验。如果浓度的95%单侧下限浓度仍高于初始浓度的90%，或者当存在任何物理不稳定迹象时仍高于初始浓度的95%（如最近所建议），则认为溶液稳定。
DEX在20至1.25mg/100mL、ALI在200至12.5mg/100mL、OND在20至1.25mg/100mL范围内校准呈线性，计算得到的相关系数（r）分别为0.998、0.999和0.999。两种混合物的批内和批间精密度均低于10%。所有制剂在储存期间物理性质稳定。按照美国食品药品监督管理局（FDA）的建议，截至30天，这些溶液浓度的下限置信度仍高于初始浓度的90%。
HPLC方法具有特异性和可重复性，可轻松用于监测DEX-ALI和DEX-OND袋生产中的质量控制。DEX-ALI和DEX-OND溶液在5±3°C下储存于聚烯烃袋中，在物理和化学性质上30天内保持稳定，因此可以提前制备。
