Cistracurium Besylate 10 mg/mL Solution Compounded in a Hospital Pharmacy to Prevent Drug Shortages: A Stability Study Involving Four Degradation Products
Autor: | Marine Roche, Cécile Danel, Nicolas Simon, Mostafa Kouach, Myriam Bouchfaa, Christophe Berneron, Pascal Odou, Damien Lannoy |
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Jazyk: | angličtina |
Rok vydání: | 2023 |
Předmět: | |
Zdroj: | Pharmaceutics, Vol 15, Iss 5, p 1404 (2023) |
Druh dokumentu: | article |
ISSN: | 15051404 1999-4923 |
DOI: | 10.3390/pharmaceutics15051404 |
Popis: | 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. Conclusion: Compounded 10 mg/mL cisatracurium injectable solution is stable for at least 15 months. |
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