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-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.
Benson
L M
LM
Biomedical Mass Spectrometry Facility, Mayo Clinic, Rochester, MN 55905.
Veverka
K A
KA
Mays
D C
DC
Nelson
A N
AN
Shriver
Z H
ZH
Lipsky
J J
JJ
Naylor
S
S
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004221:Disulfiram / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*; D010782:Photolysis; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship
D000444:Aldehyde Dehydrogenase; D004221:Disulfiram