Cistracurium Besylate 10 mg/mL Solution Compounded in a Hospital Pharmacy to Prevent Drug Shortages: A Stability Study Involving Four Degradation Products.
cisatracurium
drug compounding
drug stability
injectable
laudanosine
Journal
Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003
Informations de publication
Date de publication:
04 May 2023
04 May 2023
Historique:
received:
28
03
2023
revised:
27
04
2023
accepted:
27
04
2023
medline:
27
5
2023
pubmed:
27
5
2023
entrez:
27
5
2023
Statut:
epublish
Résumé
Stability study of a 10 mg/mL injectable cisatracurium solution stored refrigerated in amber glass ampoules for 18 months (M18). 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). 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. Compounded 10 mg/mL cisatracurium injectable solution is stable for at least 15 months.
Sections du résumé
BACKGROUND
BACKGROUND
Stability study of a 10 mg/mL injectable cisatracurium solution stored refrigerated in amber glass ampoules for 18 months (M18).
METHODS
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
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
CONCLUSIONS
Compounded 10 mg/mL cisatracurium injectable solution is stable for at least 15 months.
Identifiants
pubmed: 37242646
pii: pharmaceutics15051404
doi: 10.3390/pharmaceutics15051404
pmc: PMC10221331
pii:
doi:
Types de publication
Journal Article
Langues
eng
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