title: Simultaneous structure-activity determination of disulfiram photolysis products by on-line continuous-flow liquid secondary ion mass spectrometry and enzyme inhibition assay.
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.
authors.affiliation: Biomedical Mass Spectrometry Facility, Mayo Clinic, Rochester, MN 55905.
authors.forename: L M
authors.initials: LM
authors.lastname: Benson
authors.forename: K A
authors.initials: KA
authors.lastname: Veverka
authors.forename: D C
authors.initials: DC
authors.lastname: Mays
authors.forename: A N
authors.initials: AN
authors.lastname: Nelson
authors.forename: Z H
authors.initials: ZH
authors.lastname: Shriver
authors.forename: J J
authors.initials: JJ
authors.lastname: Lipsky
authors.forename: S
authors.initials: S
authors.lastname: Naylor
mesh_terms: 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
chemical_list: D000444:Aldehyde Dehydrogenase; D004221:Disulfiram