Stability study of a new antidote drug combination (Atropine-HI-6-Prodiazepam) for treatment of organophosphate poisoning

The main purpose of this study was to investigate the chemical stability of a new antidote combination for the treatment of organophosphate poisoning. The antidote combination was packed (enclosed) in two plastic compartments separated by a barrier film. One of them contained a powder oxime cholinesterase reactivator (HI-6-monohydrate 1-[[[4-(aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydroxyimino)methyl]-pyridinium dichloride). The other contained an anticholinergic (Atropine) and an anticonvulsant (Prodiazepam or Avizafone (L-lysyl-N-(2-benzoyl-4-chlorophenyl)-N-methyl-glycinamide dihydrochloride) drug in a liquid mixture. The plastic compartments were mounted in an autoinjector device to study the dissolution of HI-6 by ejection of the solution. Drug analysis was performed by high-performance liquid chromatography. The results obtained after 6 months show that this new antidote combination is stable. The amount of each antidote is unchanged during the study. Some known degradation products can be detected in small amounts. The autoinjector mechanism used, gives a complete dissolution of HI-6 powder in the liquid mixture throughout the study. (C) 2000 Elsevier Science B.V. All rights reserved.