The overall goal of this proposal is to acquire funds to purchase a liquid chromatographic/tandem quadrupole mass spectrometric detection (LC-MS/MS) system for analysis of novel agents and biomarkers under investigation for the treatment, risk association, and prevention of cancer. The funds will be used to purchase a Waters(r) Micromass(r) Quattro Premier(tm) XE tandem quadrupole mass spectrometer coupled with an ACQUITY UPLC(tm) chromatographic system, and the new instrument will be dedicated to support NIH-funded investigators requiring sensitive quantitative analysis. The City of Hope (COH), as an NCI-designated Comprehensive Cancer Center, provides state-of-the-art clinical and translational research-based cancer care. The Analytical Pharmacology Core Facility (APCF) of the COH 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. Overall, the APCF is used heavily by NCI-funded grants supporting Phase I trials and SWOG Early Therapeutics trials, an NCI-funded contract supporting Phase II trials, as well as peer-reviewed in-house cancer chemotherapy protocols. However, the core also supports a large number of cancer-related laboratory research projects, e.g., pre-clinical development of chemopreventive agents, basic investigations into the mechanism of chemical and UV light induced carcinogenesis, pre-clinical studies of RNA-targeted therapies, and evaluations of novel Stat-signaling targeted therapies. Thus, the APCF supports both early clinical development of anticancer drugs and pre-clinical cancer-related research, and is therefore a critical resource for the Cancer Center. Because of its importance to the Cancer Center, the APCF 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. Acquisition of a second LC- MS/MS system dedicated solely to support NIH funded research is now required to maintain the core facility as state-of-the-art, and to allow us to continue to adequately serve both funded investigators and those in pursuit of NIH funding. The addition of a second LC-MS/MS will directly benefit the NIH grant-funded early clinical and pre-clinical 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 new instrument will be housed in the current APCF laboratory space and will take advantage of existing technical and administrative oversight. ? ? ?