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

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...

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Bibliographic Details
Published in:Journal of Chromatography A 1995-02, Vol.693 (1), p.162-166
Main Authors: Benson, Linda M., Veverka, Karen A., Mays, Dennis C., Nelson, Albert N., Shriver, Zachary H., Lipsky, James J., Naylor, Stephen
Format: Article
Language:English
Subjects:
Aldehyde Dehydrogenase - antagonists & inhibitors
Chromatography, High Pressure Liquid - methods
Disulfiram - chemistry
Mass Spectrometry - methods
Photolysis
Saccharomyces cerevisiae - enzymology
Structure-Activity Relationship
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Summary: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.
ISSN:0021-9673
DOI:10.1016/0021-9673(94)01101-J