Statistical Analysis and Forensics Determination of Designer Drugs via Direct Analysis in Real Time Mass Spectrometry (DART-MS)

This proposal describes the development of Direct Analysis in Real-time (DART) mass spectrometric methods to analyze and characterize designer drugs, and in particular, emerging novel variants of synthetic cannabinoids and cathinone bath salts. The methods developed in this proposal will enable more comprehensive, rapid, and sensitive analysis for use in crime labs than is currently available, and will provide a pathway to deal with (1) sample testing backlogs; (2) determination of unknowns; (3) characterization of complex mixtures and unknowns; and (4) multivariate statistical characterization of analogs and mixtures. The past decade has witnessed the emergence of numerous designer drugs commonly known as Spice, K2 and bath salts, leading to significant new challenges for crime labs. The active ingredients in these products are synthetic cannabinoid receptor agonists and cathinone derivatives. Synthetic cannabinoid receptor agonists are small molecules that bind to the same receptors as the active ingredient in marijuana, tetrahydrocannabinol, even though they are often structurally dissimilar. Cathinone bath salts and their derivatives are alkaloids chemically similar to ephedrine and amphetamine stimulants. These designer drug compounds have been tied to large spikes in emergency room visits, numerous overdoses, and even fatalities. A small number of these substances are controlled by the DEA in response to increased instances of abuse. However, new variants continue to emerge, with differing names, various active ingredients, and a wide range of base components. Currently, detection of these compounds by law enforcement resembles a whack-a-mole effort, where once a substance is identified and regulated, multiple others that circumvent detection and regulations, and evade analog drug laws, come to light. Given that the manufacturers have demonstrated ability to rapidly modify the components and formulations, instrumentation and methodologies that can readily identify the presence of synthetic drug analogs is highly desirable. Presently, detection and characterization of the entire range of related substances by conventional methods is not practical, and the details of how to best determine their presence have not been systematically established. Crime labs are experiencing large influxes of these substances and are having difficulty identifying the myriad of closely related analogs efficiently because most of these substances are not included in any spectral library and new variants regularly are found. To address these challenges, we propose to conduct studies employing DART-MS to drastically streamline sample analysis, minimize sample preparations, and develop a series of straightforward methods to statistically characterize emerging structural analogs. The speed and efficiency of DART-MS testing of such highly unpredictable samples demonstrate that the technique can be an attractive alternative for GC- and LC-MS. Our published work on the use of this technique has demonstrated its capacity to serve as a rapid screening (preliminary) testing method, as well as a means to more comprehensively characterize the active components of designer drugs (confirmatory testing). In this proposal, we detail how a single DART-MS instrument in a forensics lab can be used for rapid and versatile analyses that would yield definitive results, while at the same time yielding substantial time-savings, lowered reagents use, cost reductions, and potentially more rapid time to prosecutions. We will develop novel methods to provide support relevant to problems currently plaguing crime labs, such as testing backlogs, mixture component determinations, and identification of illicit drug analogs. ca/ncf