UPLC with Tandem MS for Sensitive Quantitative Analysis of Small Molecules

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DESCRIPTION (provided by applicant): The overall goal of this proposal is to acquire funds to purchase a triple quadrupole mass spectrometer to replace an existing 9-year old Waters Micromass Quattro LC instrument. The funds will be used to purchase a Applied Biosystems (AB) SCIEX Triple QuadTM 5500 (API 5500) system (a tandem quadrupole mass spectrometer) coupled with an ACQUITY UPLCTM chromatographic system that will be dedicated to support NIH-funded investigators requiring sensitive quantitative analysis. A group of 9 investigators at the Johns Hopkins Medical Institutions (4 major, 5 minor) has been identified whose research (100% NIH-funded) is dependent on analyses which are only possible with the requested instrument. The Johns Hopkins University Kimmel Cancer Center (JHU KCC) is a NCI-Designated Comprehensive Cancer Center since 1976 and is part of the Johns Hopkins Medical Institute which has the Institute for Clinical and Translational Research (ICTR) Award. The JHU KCC Analytical Pharmacology Core (JHU KCC APC) is a Cancer Center shared resource that provides funded investigators with technical expertise and access to large equipment for quantitative analysis of anticancer drugs and related compounds. The ICTR has broadened access to the JHU KCC APC to non-Cancer Center members, The JHU KCC APC is used heavily by NIH-funded grants supporting both Phase I trials (U01),and preclinical research projects (e.g., preclinical development of thapsigargin prodrugs (R01), agents in Caseating Granulomas (R01), and agents in Buruli ulcers (R01)). As the JHU KCC APC supports both early clinical development of anti-cancer drugs and pre-clinical cancer-related research, it is a critical resource for the Cancer Center and the Johns Hopkins Medical Institutions. This critical resource has experienced a rapid growth in the number of basic and clinical investigators requiring analytical services. As a result, usage of the existing LC/MS/MS instrument is currently at full capacity. As Waters Corporation is terminating the Micromass Quattro LC product line, by ceasing to provide service contracts and replacement parts for this instrument in late 2009, the capacity of the JHU KCC APC will decrease substantially (50%) unless a qualified new mass spectrometer is functionally up and running in our laboratory prior to the Micromass Quattro LC being fully decommissioned. The addition of a new LC/MS/MS to replace the outdated LC/MS/MS will directly benefit NIH grant-funded early clinical and preclinical trial projects. In addition, it will indirectly benefit NIH-funded contracts and studies that are not currently NIH funded by freeing time on the existing LC/MS/MS. The LC/MS/MS capability of the JHU KCC APC will contribute to the long-range biomedical research goals of the Johns Hopkins Medical Institutions. PUBLIC HEALTH RELEVANCE: The ability to quantify drugs and their metabolites in cells, plasma, and tissues with high sensitivity and selectivity is an essential need of research projects that aim to improve the therapy of diseases or to understand the basic mechanisms of biological processes. The proposed updated analytical instrument will bring the state-of-the-art instrumentation necessary to the Johns Hopkins Medical Institutions, thereby advancing many projects that seek to improve the therapy of serious diseases such as cancer and tuberculosis.