Study on the stability of the oxime HI 6 in aqueous solution

HI 6 (Pyridinium, 1-[[[4-(aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydro xyimino) methyl]-dichloride is an effective antidote against poisoning with extremely toxic organophosphates. Because of conflicting reports on the stability of HI 6 in aqueous solutions, we studied the factors influencing its stability. HI 6 has been shown to be most stable in acidic solution between pH 2 and 3. At that pH, HI 6 decomposes probably by attack of nucleophiles on the methylene carbon atom of the animal-acetal bond of the "ether bridge". HI 6 decomposition follows first order kinetics. From Arrhenius plots of the decay of HI 6 at various concentrations it became obvious that the rate of decomposition increased with increasing HI 6 concentration with simultaneous decrease in the energy of activation. To decide whether the pyridinium compound itself or its anions are responsible for the enhanced decomposition, we studied the influence of chloride, phosphate and iodide. These anions stimulated the decay of HI 6 at increasing strength; their effect, however, was small as compared to that brought about by the pyridinium oxime itself. Since 1-methylisonicotinamide chloride had virtually no effect in contrast to 1-methylpyridinium-2-aldoxime chloride, we conclude that the oximate anion is responsible for the intermolecular attack on HI 6. At present, we recommend storage of HI 6 at concentrations not exceeding 0.1 M in aqueous solution at pH 2.5 and low temperatures. Under these conditions an apparent shelf-life of 20 years is calculated when HI 6 is stored at 8 degrees C.