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Abstract：
BACKGROUND: Stability study of a 10 mg/mL injectable cisatracurium solution stored refrigerated in amber glass ampoules for 18 months (M18).
METHODS: 4000 ampoules were aseptically compounded using European Pharmacopoeia (EP)-grade cisatracurium besylate, sterile water for injection, and benzenesulfonic acid. We developed and validated a stability-indicating HPLC-UV method for cisatracurium and laudanosine. At each stability study time point, we recorded the visual aspect, cisatracurium and laudanosine levels, pH, and osmolality. Sterility, bacterial endotoxin content, and non-visible particles in solution were checked after compounding (T0) and after M12 and M18 of storage. We used HPLC-MS/MS to identify the degradation products (DPs).
RESULTS: During the study, osmolality remained stable, pH decreased slightly, and the organoleptic properties did not change. The number of non-visible particles remained below the EP\'s threshold. Sterility was preserved, and bacterial endotoxin level remained below the calculated threshold. Cisatracurium concentration remained within the ±10% acceptance interval for 15 months and then decreased to 88.7% of C0 after M18. The laudanosine generated accounted for less than a fifth of the cisatracurium degradation, and three DPs were generated-identified as EP impurity A, impurities E/F, and impurities N/O.
CONCLUSIONS: Compounded 10 mg/mL cisatracurium injectable solution is stable for at least 15 months.
METHODS: 4000 ampoules were aseptically compounded using European Pharmacopoeia (EP)-grade cisatracurium besylate, sterile water for injection, and benzenesulfonic acid. We developed and validated a stability-indicating HPLC-UV method for cisatracurium and laudanosine. At each stability study time point, we recorded the visual aspect, cisatracurium and laudanosine levels, pH, and osmolality. Sterility, bacterial endotoxin content, and non-visible particles in solution were checked after compounding (T0) and after M12 and M18 of storage. We used HPLC-MS/MS to identify the degradation products (DPs).
RESULTS: During the study, osmolality remained stable, pH decreased slightly, and the organoleptic properties did not change. The number of non-visible particles remained below the EP\'s threshold. Sterility was preserved, and bacterial endotoxin level remained below the calculated threshold. Cisatracurium concentration remained within the ±10% acceptance interval for 15 months and then decreased to 88.7% of C0 after M18. The laudanosine generated accounted for less than a fifth of the cisatracurium degradation, and three DPs were generated-identified as EP impurity A, impurities E/F, and impurities N/O.
CONCLUSIONS: Compounded 10 mg/mL cisatracurium injectable solution is stable for at least 15 months.
摘要：
背景：在琥珀色玻璃安瓿中冷藏保存18个月（M18）的10mg/mL可注射顺式阿曲库铵溶液的稳定性研究。
方法：使用欧洲药典（EP）级苯磺酸顺式阿曲库铵无菌复合4000安瓿，无菌注射用水,和苯磺酸。我们开发并验证了用于顺式阿曲库铵和laudanosine的稳定性指示HPLC-UV方法。在每个稳定性研究时间点，我们记录了视觉方面，顺式阿曲库铵和laudanosine水平，pH值,和渗透压。无菌,细菌内毒素含量，在混合后(T0)和储存的M12和M18后,检查溶液中的不可见颗粒。我们使用HPLC-MS/MS来鉴定降解产物(DP)。
结果：在研究期间，渗透压保持稳定,pH值略有下降，感官特性没有改变。不可见颗粒的数量保持在EP的阈值以下。无菌保存下来,细菌内毒素水平仍低于计算的阈值。顺式阿曲库铵浓度在15个月内保持在±10％接受间隔内，然后在M18后降低至C0的88.7％。产生的laudanosine占顺式阿曲库铵降解的不到五分之一，产生了三个DP，鉴定为EP杂质A，杂质E/F，和杂质N/O.
结论：复配10mg/mL顺式阿曲库铵注射液至少15个月是稳定的。
方法：使用欧洲药典（EP）级苯磺酸顺式阿曲库铵无菌复合4000安瓿，无菌注射用水,和苯磺酸。我们开发并验证了用于顺式阿曲库铵和laudanosine的稳定性指示HPLC-UV方法。在每个稳定性研究时间点，我们记录了视觉方面，顺式阿曲库铵和laudanosine水平，pH值,和渗透压。无菌,细菌内毒素含量，在混合后(T0)和储存的M12和M18后,检查溶液中的不可见颗粒。我们使用HPLC-MS/MS来鉴定降解产物(DP)。
结果：在研究期间，渗透压保持稳定,pH值略有下降，感官特性没有改变。不可见颗粒的数量保持在EP的阈值以下。无菌保存下来,细菌内毒素水平仍低于计算的阈值。顺式阿曲库铵浓度在15个月内保持在±10％接受间隔内，然后在M18后降低至C0的88.7％。产生的laudanosine占顺式阿曲库铵降解的不到五分之一，产生了三个DP，鉴定为EP杂质A，杂质E/F，和杂质N/O.
结论：复配10mg/mL顺式阿曲库铵注射液至少15个月是稳定的。
