As submitted by the proposer: The purpose of this project is to investigate the use of ultra-high performance supercritical fluid chromatography (UHPSFC) as a separation technique for forensic drug analysis, using synthetic cannabinoids and bath salts as model compounds. The goal of this research would be to establish UHPSFC as an accepted technique. Seized drugs can be complex mixtures consisting of natural products or powders containing the seized drug, impurities, adulterants and diluents. For the analysis of these exhibits, highly sophisticated separation techniques would be desirable. The present techniques accepted by the forensic community (i.e., SWGDRUG), including TLC, GC, LC (HPLC, UHPLC) and CE, can fail to have adequate chromatographic performance or instrument reliability. The recently introduced separation technique UHPSFC produces highly efficient separations performed on a new generation of analytical SFC instruments with green mobile phases containing primarily carbon dioxide, that have properties intermediate between a liquid and a gas. GC is disadvantageous for solutes that are thermally labile, polar and non-volatile. UHPSFC as is the case of LC and CE is compatible with the above solutes. However, UHPSFC compared to LC offers at least 4X times the separation speed and increased selectivity, especially for similar solutes. Similar to LC, UHPSFC is a considerably more rugged technique than CE. For this project Professor Bruce McCord of Florida International University and Doctor David Northrop of the Washington State Patrol will serve as advisors. All experiments will be conducted at George Washington University with Waters providing an UHPSFC instrument equipped with both UV-PDA and single Quad MS detection capabilities. Emerging drugs, such as synthetic cannabinoids and bath most commonly consist of similar solutes, many of which are bad actors by GC. For the first year optimized UHPSFC separations will be developed. In addition, figures of merit including repeatability, reproducibility and selectivity will be measured using standard statistical analysis. In the second year the separation capabilities of UHPSFC will be compared with GC and UHPLC for emerging drugs. In addition, 40 simulated samples will be analyzed to test the accuracy of UHPSFC for the determination of emerging drugs in various sample matrixes. Data developed from this study will be disseminated by peer reviewed publications, web based protocols and scientific presentations at meetings. The acceptance of UPSFC as viable technique would significantly enhance forensic drug analysis.