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Detection and prevention of aggregate formation of cobinamide as an antidote for cyanide poisoning


Cobinamide, a vitamin B12 precursor, has a high affinity for cyanide and is an effective antidote for cyanide poisoning in animal models. However, when given as an intramuscular injection at high concentrations, the compound forms aggregates that both inhibit its absorption and damage the surrounding muscle tissue. The objective of this study is to investigate aggregate formation in terms of aggregate number and thermodynamics of formation as a means to prevent aggregate formation in the drug formulation. Cobinamide solutions ranging in concentrations from 5[mu]M to 1mM were scanned from 400nm to 600nm at 25°C, 35°C, 45°C, and 65°C using a spectrophotometer. The spectrum within this range was representative of aggregate formation as visible changes were observed with increasing concentrations and temperatures. A variety of compounds were tested for their ability to prevent aggregate formation. We analyzed the effect of temperature on the stability of the aggregated compounds. Our results show that cobinamide forms very strong aggregates that can be largely prevented using malic acid

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