Studies on the stability and decomposition of the Hagedorn-oxime HLö 7 in aqueous solution

Arch Toxicol. 1989;63(1):59-67. doi: 10.1007/BF00334636.

Abstract

HLö 7, (pyridinium, 1-[[[4-(aminoarbonyl)pyridinio]methoxy]methyl] -2,4-bis- [(hydroxyimino)methyl] diiodide) has been shown to be efficacious in soman poisoning of mice even in the absence of atropine. To assess possible risks involved in the administration of HLö 7 its degradation products were analyzed at pH 2.5 and pH 7.4, respectively. At pH 2.5, where HLö 7 in aqueous solution was assumed to possess maximal stability, the predicted shelf life (10% decomposition) was about 8 years for 10 mM solutions at 8 degrees C. The apparent energy of activation was 117 kJ/mol. At pH 2.5, attack on the aminal-acetal bond predominated with formation of pyridine-2,4-dialdoxime, 2-cyanopyridine-4-aldoxime, isonicotinamide, and formaldehyde. At pH 7.4, primary attack on the 2-aldoxime group resulted in formation of an intermediate 2-cyano-4-aldoxime derivative which mainly decomposed into cyanide and the corresponding 2-pyridinone, 1-[[[4-(aminocarbonyl)-pyridinio]methoxy]methyl]-4- [(hydroxyimino)methyl] diiodide. In addition, liberated cyanide reacted with the intermediate 2-cyano-4-aldoxime derivative with formation of 2-pyridinone, 1-[[[4-(aminocarbonyl)-pyridinio]-methoxy]methyl]-6-cyano-4- [(hydroxyimino)methyl] diiodide. This cyanide sequestering pathway became significant only at high concentrations (10 mM) of HLö 7, and was marginal at 1 mM HLö 7.

MeSH terms

  • Chromatography, High Pressure Liquid
  • Cyanides
  • Cyclohexanones
  • Drug Stability
  • Hydrogen-Ion Concentration
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Pyridines / analysis*
  • Pyridinium Compounds / analysis*
  • Solutions
  • Spectrophotometry, Infrared

Substances

  • Cyanides
  • Cyclohexanones
  • Pyridines
  • Pyridinium Compounds
  • Solutions
  • HLo 7
  • dimedone