Simultaneous structure-activity determination of disulfiram photolysis products by on-line continuous-flow liquid secondary ion mass spectrometry and enzyme inhibition assay

J Chromatogr A. 1995 Feb 17;693(1):162-6. doi: 10.1016/0021-9673(94)01101-j.

Abstract

Disulfiram (DSF) is used in the treatment of recovering alcoholics and exerts its effect by inhibiting the enzyme aldehyde dehydrogenase (ALDH). We analyzed a mixture of products derived photochemically from DSF with on-line microbore HPLC-continuous-flow liquid secondary ion mass spectrometry (HPLC-CF-LSI-MS). By utilizing the post-HPLC column split of solvent flow, a small proportion (ca. 5%) was sent directly into the mass spectrometer, and the remainder was collected. Simultaneous MS analysis and enzyme inhibition studies on ALDH were then possible. Furthermore, using HPLC-CF-LSI-MS-MS, we were able to structurally characterize an interesting sulfine compound that inhibited ALDH.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aldehyde Dehydrogenase / antagonists & inhibitors*
  • Chromatography, High Pressure Liquid / methods*
  • Disulfiram / chemistry*
  • Mass Spectrometry / methods*
  • Photolysis
  • Saccharomyces cerevisiae / enzymology
  • Structure-Activity Relationship

Substances

  • Aldehyde Dehydrogenase
  • Disulfiram