A wide variety of projects in biomedical research require separating compounds by high performance liquid chromatography (LC) and subjecting these isolated species to structure analysis by mass spectrometry (MS). The development of thermospray techniques have greatly facilitated the interfacing of these instruments, so that online mass spectral analysis of chromatographic effluents can now be accomplished routinely. At the present time, however, no LC/MS system is available to the scientific community in the State of Colorado. Recognizing the potential of this technique for enhancing their research, a group of 10 PHS-supported investigators from the University of Colorado (Boulder), the University of Colorado Health Sciences Center (Denver), the AMC Cancer Research Center (Denver) and Colorado State University (Fort Collins), have described their plans for utilizing LC/MS if a shared instrument was purchased as a result of this application. A secondary user group of 4 investigators (supported be 4 PHS grants) has been identified also. Specific applications of LC/MS to the funded research of the user groups include analyses of (1) reactive and potentially toxic species (catechols, quinones, peroxides and unsaturated aldehydes) produced during the metabolism of aromatic compounds and during lipid peroxidation, (2) glutathione conjugates of reactive metabolites, (3) DNA adducts formed by interactions with toxic chemicals and anti-cancer drugs, (4) anthracyclines, (5) fragments of peptide neurotransmitters, (6) oligosaccharides, (7) glycolipids and (8) phospholipids. The strength of the LC/MS technique is in the analysis of compounds such as these that are nonvolatile, unstable or present in very low concentrations. The user group proposes to install an LC/MS system in the School of Pharmacy on the campus of the University of Colorado, Boulder. This is the most convenient location for the majority of users, and will be maintained by a group that has successfully maintained a gas chromatograph-mass spectrometer for several years. An internal advisory committee has been organized to assist the principal investigator, and a viable plan has been proposed to assure the long-term operation of a shared instrument.
