Project Summary The Substance Abuse and Mental Health Services Administration (SAMHSA) has set guidelines for illicit drug monitoring for both screening and confirmatory tests. Point-of-care (POC) screening assays usually rely upon immunoassays that lack specificity among compounds in a given drug class. Confirmation testing usually employs chromatography coupled to mass spectrometry (MS), which is a powerful technique capable of identifying the relevant analytes of interest in complex samples; however, this approach requires large, expensive equipment that requires technical expertise to operate, thus precluding it from POC environments. In this Fast-Track SBIR project, scientists at Axcend Corporation in collaboration with chromatography and drug analysis experts in academia and advice from practicing health care professionals will pursue further development of a compact capillary liquid chromatography (LC) platform for rapid POC screening of drugs of abuse. In Phase I, sample preparation with a novel solid phase extraction (SPE) apparatus will be optimized and automated, a longer pathlength UV absorption detector flow cell will be created, and capillary LC stationary phases and mobile phases will be investigated and selected to achieve SAMHSA testing concentration cutoff limits for relevant compounds using the compact LC system. In Phase II, novel column-column and column- detector combinations, diode-array detection modules, and data processing approaches combining chromatographic retention times and UV absorption ratios will be developed to enhance the analysis of these compounds and provide timely information to support urgent patient treatment decisions. Key aspects of this proposal that are unique to advancing the field of POC chemical analysis using capillary LC are (1) improved sensitivity using novel simple off-line and on-line extraction and concentration devices, and a longer pathlength UV-absorption flow cell; (2) combinations of columns, solvents, and modes of operation for maximum LC separation, and (3) enhanced selectivity of detection using innovative tandem column–UV-detector combinations, (4) a new compact DAD UV-absorption detector for capillary LC, and (5) unique data handling software algorithms for peak deconvolution. These innovations are new to the area of POC analysis as well as to the broad field of capillary LC in general. The results from this project will be a critical step towards the release of a POC drug screening solution that provides improved patient care compared to current healthcare practices.