Support for a triple quadruple (QqQ) mass spectrometer with associated liquid chromatography equipment that is essential to many NIH funded research programs is requested. This is a resubmission with an introduction that specifically answers points raised in the previous Summary Statement, in particular those concerns as to the operation of the system in an Open Access environment. There is no LC-QqQ-MS available in the UC Irvine Mass Spectrometry Facility. Current and developing research projects that are dependent on quantification are being stalled by the lack of an LC-QqQ-MS system. The projects are spread across the Schools of Physical Sciences and Biological Sciences and the College of Medicine and the instrument will, therefore, be truly a shared inter-disciplinary resource. Research projects of the major users include: a) Dr. Van Vranken: the role of ditryptophan and other crosslinked species in the aging of proteins with particular respect to the formation of cataracts, b) Dr. Blumberg: steroid and xenobiotic receptor (SRX) ligand behavior including interspecies response differences and ligand combinations in receptor activation, c) Dr. Farmer: molecular trap based assays for HNO and related species at physiologically relevant concentrations, d) Dr. Piomelli: quantification of acylethanolamides for elucidating their role as cannabinoid receptor ligands and in cellular signaling, e) Dr. Tsai; studies on the synthesis of polyketides and associated deoxysugars as mediated enzymatically via polyketide synthase, f) Dr. Weiss: kinetic experiments for understanding the synthetic capabilities of enzyme variants (>1010) generated through DNA manipulation followed by phage display expression. Minor users and other NIH funded research groups will be provided access to this LC-QqQ-MS. To ensure maximum usage and proper maintenance the instrument will be placed it in the UCI Mass Spectrometry Facility. The Facility Director has over 25 years experience in the field. The Facility is well equipped and heavily used for qualitative applications. However, the projects in this application require quantification for which the Facility is ill-equipped. The Facility is effectively using Open Access technology, e.g., 20,000 samples on a single loop injection ESI instrument in 2003 along with C 18-LC-ESI-MS and GC-MS on other instruments. The requested instrument will be Open Access but with a modified approach for quantitative analysis (see Introduction). Additional operational funding is obtained though charges to the user community's grants.
