Ultra-performance liquid chromatography - triple quadrupole mass spectrometry system

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PROJECT SUMMARY The University of Arizona is requesting funds for the acquisition of an ultra-performance liquid chromatography – triple quadrupole mass spectrometry system (triple quadrupole UPLC/MS). The instrument will be operated within the framework of the University of Arizona Cancer Center, Analytical Chemistry Shared Resource (UACC, ACSR) to support 12 NIH-funded researchers, including 10 UACC investigators, and new users. ACSR is a shared resource funded by the UACC Cancer Center Support Grant (CCSG) since 2001 to provide centralized support in performing chromatography-mass spectrometry based assays for quantitative measurements of drugs, novel therapeutics, nutraceuticals, bioactive food components, carcinogens, toxicants, and endogenous metabolites in various biological specimens, as well as qualitative studies in untargeted metabolomics and lipidomics. It has a proven track record of providing support to UACC investigators and campus-wide users and has received an “Outstanding” merit in the National Cancer Institute’s CCSG review. Users listed in this application have past and/or ongoing projects supported by the ACSR. The triple quadrupole LC/MS is considered the gold standard for rapid development, validation, and implementation of analytical chemistry assays to enable highly sensitive and specific quantitative analysis of small molecule analytes in complex biological samples. The primary need for the instrument is to replace an aging instrument (Quantum Ultra triple quad acquired in 2005) no longer supported by the manufacturer. ACSR supports projects from an average of 30 investigators annually and is still using this aging equipment today to support roughly 40% of projects. In addition to replacing the aging instrument, the requested instrument also offers an improved assay sensitivity into the ppt range and beyond and has a wider mass range expanding the analysis of peptides. With the ultrahigh scan speeds combined with dynamic multiple reaction monitoring, the requested instrument can also support comprehensive, high-throughput, targeted lipidomics analysis. Finally, the upgraded UPLC will enhance both capability and capacity, via shorten run time and superior separation compared to our current system. The instrument will support the assessment of the systemic bioavailability and tissue distribution of novel therapeutics and preventive interventions, the measurements of the extent of systemic and target tissue carcinogen/toxicant exposure, the measurement of endogenous metabolites in biofluids and tissues as surrogate risk and/or end- point biomarkers and for assessment of metabolic changes to define the mechanisms underlying the disease of interest and to develop new strategies for treatment. Incorporation of the requested instrument into a well- established shared resource will promote cost effectiveness, encourage optimal sharing among users, and foster a collaborative multidisciplinary environment. We strongly believe that the requested instrument will have a significant impact on NIH-funded basic, translational, and clinical research at the University of Arizona and contribute to the institution’s continued success in biomedical research.