versión impresa ISSN 1887-8571
SANCHEZ RAMOS, J.J.. Stability of hydroxocobalamin in water for injection as cyanide antidote. Sanid. Mil. [online]. 2012, vol.68, n.2, pp.87-96. ISSN 1887-8571. http://dx.doi.org/10.4321/S1887-85712012000200005.
Background: Cyanide has been used as an agent for chemical warfare, and today it is also a credible terrorism threat agent. Cyanide poisoning is the first cause of death in victims of smoke inhalation from enclosed space fires. Successful treatment for acute cyanide poisoning depends upon rapid antidotes administration, and fixation of the cyanide ion by antidotes. Hydroxocobalamin seems to be a more appropriate antidote than sodium nitrite for empiric treatment of smoke inhalation and other suspected cyanide intoxication victims in the out-of-hospital setting. Stability of hydroxocobalamin in water for injection at cyanide antidote dose has been studied throughout the time and in four types of containers. Methods: The parenteral solution was prepared by aseptic procedures without terminal sterilization, and according to the United States Pharmacopoeia (USP) specifications. Four types of primary containers were used: glass ampoules, semi-rigid polypropylene bags and vials, and rigid plastic vials made of COC. Hydroxocobalamin content and other parameters from the studied solutions, conserved at 4o C, 25o C and 37o C was carried out using molecular spectrometry, liquid-liquid chromatography and others assays. Results: A 4o C the hydroxocobalamin content in the studied samples was invariable (mean 99,81% ± 0,69%; p = 0,95; n = 7; t = 472 days). Very similar results were obtained for samples at 25o C (mean 100,85% ± 1,79%; p = 0,95; n = 6; t = 353 days). At 37o C there was an small decrease in the ampoules hydroxocobalamin content (mean = 92,87% ± 6,08%; p = 0,95; n = 4; t = 472 days). The solution in polypropylene bags suffered a concentration due to water permeation through the container. Both types of vials had hydroxocobalamin contents in the USP specifications (95-115%). Steam sterilization at 115o C for 30 minutes turned hydroxocobalamin content out of specifications. Conclusion: The parenteral solution of hydroxocobalamin in water for injection at the dose of NBC cyanide antidote, ready to use, is stable at temperature below 25oC, at least for 15 months. Because of the chemical inertia and physical properties, the polypropylene vials are the more appropriated containers for this parenteral solution, which has to be prepared by aseptic procedures without terminal sterilization.
Palabras clave : Hydroxocobalamin injection; Hydroxocobalamin stability; Cyanide antidotes; NBQ; Terrorism; Chemical warfare; Smoke inhalation.