This shared instrumentation proposal requests funding to purchase an AB Sciex QTRAP 6500 triple quadrupole / linear ion trap mass spectrometer with two inlets - an Agilent 1290 ultra-high pressure liquid chromatography (UHPLC) and a Thermo/Dionex UltiMate 3000 RSLCnano LC Nano-liquid chromatography systems. The instrumentation will be housed in the Integrated Molecular Structure Education and Research Center (IMSERC) and will enable the quantitation of small molecule drug candidates, metabolites, and peptides by research groups for basic science / drug delivery applications and will be utilized by three other core facilities at Northwestern University (NU). The Developmental Therapeutic Core (DTC) will use this instrument to quantify metabolites from animal studies in order to perform lead optimization, the Mary Beth Connelly Clinical Pharmacology Core will use the instrument to perform pre-clinical and early phase clinical pharmacokinetics studies to determine dosing strategies for new drugs and the Proteomics Center of Excellence (PCE) will use this instrument to perform peptide quantitation studies to understand signaling pathways an cancerous tumors. Locating the proposed instrument in a central user facility with a long history of housing shared instrumentation will allow all of the cores and researchers to take advantage of the capability (rather than duplicating resources across the university) yet still have the experts in each core facility assist research groups with experiment design, manage the studies and provide detailed analysis of results. The AB Sciex QTRAP 6500 will support eight active, NIH funded projects related to diabetes (Bass), infectious disease/AIDS (Kiser), nervous system diseases (Watterson/ Siddique), oncology/cancer (Wainwright / Schiltz) and parasitology (Engman). These MS based studies are already underway today. However, the 7 year old Thermo TSQ QQQ mass spectrometer in PCE is oversubscribed and lacks sensitivity for some experiments, the 12 year old AB Sciex API3000 is officially obsolete as of 2007 and taken care of on a best effort basis only and IMSERC's AmaZonX ion trap instrument lacks sensitivity and is not designed for rapid chromatography experiments. The paucity of state-of-the-art capabilities at NU have forced groups to either send samples out to contract research laboratories at great expense and frequently results in limited feedback rather than using a collaborative project. Northwestern University has a comprehensive infrastructure and track record of translating small molecule compounds and nanoconstructs from discovery to clinical stages of development for use as molecular probes and therapeutics. This proposed mass spectrometer will greatly increase the efficiency of this process as studies are able to be completed on site in a rapid, collaborative model.
; The ability to accurately identify and quantify levels of prodrugs, active ingredients and metabolites in cells, plasma and elimination paths is an essential need of scientists and clinicians working to develop novel therapeutics and molecular probes for the early detection of diseases. A Triple quadrupole mass spectrometer is the gold standard for this type of measurement. This proposal requests a new state-of-the-art triple quadrupole/ linear ion trap mass spectrometer that will provide broad access to this technique and allow for the eventual retirement of NU's 11 year old, obsolete triple quadrupole mass spectrometer.
| Wang, Xiaodi; Kalow, Julia A (2018) Rapid Aqueous Photouncaging by Red Light. Org Lett 20:1716-1719 |
