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 cholines terase reactivator (HI-6-monohydrate 1-[[[4-(aminocarbonyl)pyridinio]methox y]methyl]-2-[(hydroxyimino)methyl]-pyridinium dichloride). The other contai ned an anticholinergic (Atropine) and an anticonvulsant (Prodiazepam or Avi zafone (L-lysyl-N-(2-benzoyl-4-chlorophenyl)-N-methyl-glycinamide dihydroch loride) 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 chromatogr aphy. The results obtained after 6 months show that this new antidote combi nation is stable. The amount of each antidote is unchanged during the study . Some known degradation products can be detected in small amounts. The aut oinjector mechanism used, gives a complete dissolution of HI-6 powder in th e liquid mixture throughout the study. (C) 2000 Elsevier Science B.V. All r ights reserved.