Megan Glasheen, Adriano Chan, Gerry R. Boss
Apr 1, 2012
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Quality indicators
Journal
The FASEB Journal
Abstract
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 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 5μM 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 to determine the heat of formation of the complexes. Our results show that cobinamide forms very strong aggregates that can be largely prevented using carboxylic acids.