The overall goal of this proposal is to acquire funds to purchase a triple quadrupole mass spectrometer to replace a recently decommissioned 11.5-year old Applied Biosystems (AB) SCIEX API3000 Triple Quad LC instrument. The funds will be used to purchase an AB SCIEX Triple Quad 4500 system (a tandem quadrupole mass spectrometer) coupled with a Shimadzu Nexera UHPLC chromatographic system that will be dedicated to support NIH-funded investigators requiring quantitative analysis. A group of investigators at the Johns Hopkins and Mid-Atlantic Shared Resources Consortium Institutions (4 major, 3 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 Sidney Kimmel Comprehensive Cancer Center (JHU SKCCC) is a NCI-Designated Comprehensive Cancer Center since 1976. The JHU SKCCC Analytical Pharmacology Core (JHU 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 JHU APC is used heavily by NIH-funded grants supporting the conduct of clinical trials in cancer patients with promising new therapies (UM1), AIDS malignancies (U01), with brain tumors (UM1) or late-stage development (U10). The JHU APC also supports preclinical research projects, e.g., preclinical development of GCPII inhibitors (R01) and preclinical projects from SPOREs (P50s) and the Mid-Atlantic Shared Resource Consortium (P30s). As the JHU 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 and Mid-Atlantic Shared Resource Consortium (MASRC) 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. An API3000 was fully decommissioned in December 2013 after over 11.5 years of service since ABSciex made the API3000 product line obsolete by ceasing to provide service and replacement parts for this instrument. Therefore, the capacity of the JHU APC has decreased substantially (by ~33%) until a qualified new mass spectrometer is functionally up and running in our laboratory. The addition of a new LC/MS/MS to replace the outdated LC/MS/MS will directly benefit NIH grant-funded early clinical trial and preclinical projects.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 APC will contribute to the long-range biomedical research goals of the Johns Hopkins and Mid-Atlantic Shared Resource Consortium (MASRC) 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 very reliable and robust 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 its complications.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
Biomedical Research Support Shared Instrumentation Grants (S10)
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Special Emphasis Panel (ZRG1-BCMB-D (30))
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Levy, Abraham
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Johns Hopkins University
Internal Medicine/Medicine
Schools of Medicine
United States
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Converse, Paul J; Almeida, Deepak V; Tasneen, Rokeya et al. (2018) Shorter-course treatment for Mycobacterium ulcerans disease with high-dose rifamycins and clofazimine in a mouse model of Buruli ulcer. PLoS Negl Trop Dis 12:e0006728