Waters Xevo TQ-XS system

Project Summary/Abstract The Bioanalytics Core laboratory at the University of Louisville Diabetes and Obesity Center (DOC) and other laboratories on campus operate mass spectrometers dedicated to meeting the ever-increasing and complex needs of NIH-funded investigators. These needs far exceed current capabilities, with major limitations comprising

a lack of ability for ultrasensitive targeted analyses in the areas of exposomics, metabolomics, and lipidomics. These applications are central to Major and Minor Users, including five NIH-funded centers and twenty-two individual research projects focusing on environmental toxicology, cardiovascular, hepatic and metabolic

disease, exercise science, and immunology. We propose to add an ultrasensitive, robust Waters Xevo TQ-XS triple-quadrupole mass spectrometer with the Acquity I-Class Premier ultraperformance liquid chromatography, which will address the analytical needs of major and minor users by significantly enhancing breadth of analyte

coverage and sensitivity of targeted bioanalyses, currently out of reach with available LC-MS instruments available at the University Campus. The proposed system will complement current bioanalytical instrumentation, currently at full capacity, and provide needed hardware to develop and transfer high-throughput, ultrasensitive

targeted methods to cater to the needs of our users. Specifically, we will set up: i) A platform to quantify ultralow- level xenobiotic adducts with mercapturic acid and carnosine to aid human exposomics studies; ii) A targeted method for urinary biogenic volatile organic compound metabolites; iii) A workflow for measurement of bile acids;

iv) specific targeted lipidomics assays (major lipid classes, short-chain fatty acids, and isoprostanes respectively); v) Quantification of corticosteroids, including cortisol and cortisone, as markers of chronic vi) A targeted assay for catecholamines and their metabolites in plasma; vii) A method to quantify reactive carbonyls

in tobacco product aerosols; viii) quantification of gut microbial amine metabolites; ix) A high-throughput assay for measuring amino acids and dipeptides in various biological matrices. Proposed work with the instrument includes detailed training and education in mass spectrometry and method development, which will further

advance research in the Center and maximize the utility of the proposed system. The DOC has the infrastructure to maintain and support the new equipment backed by the support of the University.