Formation of 2,6-dimethoxy-1,4-benzoquinone, a highly genotoxic compound, from the reaction of sodium nitrite with the sympathomimetic drug dimethophrine in acidic aqueous solution

Farmaco Sci. 1988 Jun;43(6):523-38.

Abstract

Because of the genotoxic effects shown by Dimethophrine (DMP) nitrosation mixtures, the interaction between DMP hydrochloride and sodium nitrite in acidic aqueous solution at 37 degrees was investigated in a wide range of reagent concentrations and molar ratios, reaction times and pH values. Actually, depending on the operating conditions, it was possible to detect variable amounts of 2,6-dimethoxy-1,4-benzoquinone (DMBQ), a highly genotoxic compound, but no N-nitrosoderivative. The highest conversion of DMP into DMBQ was obtained when concentrated acidic solutions of DMP and NaNO2 (molar ratio 1:1.9) reacted at pH 3.0-4.0 (50-60% after 1 hour, depending on the pH conditions). When DMP hydrochloride and NaNO2 (molar ratio 1:0.95) were allowed to react at pH 3.5 in a more diluted solution, to mimic gastric conditions, the conversion of DMP into DMBQ after 20 min was about 3%. The breakdown of DMP can be prevented by adding suitable amounts of ascorbic acid to the reagents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoquinones*
  • Chemical Phenomena
  • Chemistry
  • Chromatography, High Pressure Liquid
  • Ethanolamines / analysis*
  • Mutagens / chemical synthesis*
  • Nitrites / analysis*
  • Quinones / chemical synthesis*
  • Quinones / toxicity
  • Sodium Nitrite / analysis*
  • Spectrophotometry, Infrared
  • Sympathomimetics / analysis*

Substances

  • Benzoquinones
  • Ethanolamines
  • Mutagens
  • Nitrites
  • Quinones
  • Sympathomimetics
  • 2,6-dimethoxy-1,4-benzoquinone
  • dimethophrine
  • Sodium Nitrite