The purpose of this proposal is to provide a second dedicated UPLC-MS/MS instrument to the established Clinical Pharmacology and Analytical Chemistry Core (CPACC) of the University of North Carolina at Chapel Hill (UNC-CH) Center for AIDS Research (CFAR). The CPACC has an 11-year record of providing a state-of- the-art centralized CLIA-certified unit to sustain the pharmacology and analytical studies of HIV/AIDS related clinical and basic science research at UNC-CH, the collaborating institutions of Family Health International and Research Triangle Institute, and to extramural CFARs. The success of the CPACC is best exemplified by the outstanding score it received from peer reviewers during the UNC CFAR's five-year renewal in 2005 for support of domestic and international investigators through analytical innovation. Since that time, the CPACC has continued to grow, and now assists more than 50 users per year. The CPACC has demonstrated success on the Agilent 6410A Triple Quadrupole LC-MS/MS System purchased in 2007. This instrument is being used full-time for network HIV prevention studies. Because of this workload, and due to lack of additional instrumentation, other key projects requiring MS/MS technology (eg humanized mouse model pharmacology for HIV prevention and cure, cellular pharmacology of antiretrovirals in the genital tract) are either on hold, or are being turned down. The addition of a second UPLC-MS/MS instrument will support NIH-funded CFAR investigators to ensure that their projects can be completed quickly and efficiently, will create job opportunities for those in the Research Triangle Area, will provide capital to local businesses, and build a foundation for longer-term economic growth within the UNC-CH system. A cost recovery fee plan guarantees the financial viability for the instrument. Dr. Angela DM Kashuba (Director of the CPACC) serves as PI of the proposal and will be responsible for all aspects of instrument maintenance and efficient usage in generating new bioanalytical innovations. The instrument will be housed in the School of Pharmacy with the other analytical instruments of the CPACC.