The overall objective of Core A is to provide analytical support to Projects 1, 2, and 3 and the Probe and Pharmaceutical Optimization Core (Core B). Core A is an integral part of the center by providing advanced analytical support, training, and cutting edge analytical techniques for drug and biomarker detection. More specifically, Core A will develop methods for the detection of target compounds and their metabolites by LC-MS or GC-MS and provide QC analysis of standard solutions prior to their use in projects. Detailed rodent ADME studies for the anticonvulsants and neuroprotectants will be performed to assist the center projects in dose selection. Core A will work with Project 2 in the identification of biomarkers of seizure as a biochemical test of how therapeutic efficacy. Metabolomics techniques, both targeted and global will be employed. Targeted metabolomics will focus on both oxylipins and neurosteroids since levels in both pathways are altered after a seizure. Global metabolomics, as a broader approach, can identify biomarkers of seizure and therapy if needed. Current methods of detection of tetramethylenedisulfotetramine (TETs) are insensitive. TETs seems like an ideal candidate for an immunoassay, since it has several heteroatoms to provide recognition points for the antibody. An additional benefit of immunoassay is its potential to be packaged in a field deployable platform for on-site detection. When there is a clear need, immunoassays to other toxins and their metabolites will be created. Objective-1: Provide general analytical support using GC-MS or LC-MS for the detection of toxins or drugs and their metabolites in biological matrices and formulations. Objective-2: Determine the metabolomic profiles of brain tissue from Projects 1 and 2 as biomarkers of seizure damage for use in assessing neuroprotective efficacy of candidate therapeutics. Objective-3: Develop innovative immunoassay methods for detection of TETs in biological and environmental matrices.
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