As submitted by the proposer: "Designer drugs" (also known as "emerging drugs of abuse") are derivatives of controlled substances that are sold on the street in an attempt to circumvent the legal restrictions placed on scheduled drugs. For multiple reasons, these drugs present a major challenge to forensic toxicologists engaged in their detection and analysis and to clinicians involved in diagnosis and treatment of their effects in both acute overdose and chronic abuse scenarios. There are currently no validated analytical methods capable of screening and/or confirming a major portion of the universe of designer drugs in forensic specimens, or for detecting and characterizing novel, newly introduced drugs. With the ongoing rise in novel drug popularity and increasing reports of adverse health effects of designer drugs, there is a clear need within the forensic toxicology community for such methods. This two-year applied research project will investigate the use of low- and high-resolution mass spectrometric techniques, stand-alone or in combination, for comprehensive screening/confirmation of designer drugs in forensic specimens. Project goals include construction of a master drug database, a high-resolution, high-mass-accuracy MS spectral library, and a triggered MRM MS database for a minimum of 500 individual designer drug entities and metabolites from the cannabinoid and stimulant classes. Validated analytical methods will be developed using state-of-the-art LC-QqQ-MS and LC-QTOF-MS instrumentation. Research will also compare several specimen extraction methods and develop an optimized specimen processing approach for designer drugs. Finally, the validated extraction and analytical methods will be tested for screening/confirmation and unknown drug identification purposes using 400 authentic urine and 100 authentic whole blood specimens. The project goals will be facilitated by a partnership with a large, high-complexity drug testing laboratory located in South Florida, who will supply authentic specimens from employment and general drug screening, physician offices, drug rehabilitation programs, and other compliance/monitoring purposes. Results of this project will be disseminated through interim and final progress reports prepared for the sponsor, reports prepared for third party entities, and presentation of data at national and international forensic science conferences and in peer-reviewed forensic/toxicology journals. It is anticipated that successful achievement of the project goals will provide working forensic toxicology labs with valuable tools for analysis of this important class of drugs, in addition to shedding light on the prevalence of designer drugs in forensic specimens obtained from the general user population.