Retrospective Identification of Synthetic Cannabinoids in Forensic Toxicology Casework using Archived High Resolution Mass Spectrometry Data

As submitted by the proposer: Since 2008, there has been a steady influx of "herbal incense", and other related botanical products sprayed with synthetic cannabinoids infiltrating the drug market. More than 160 synthetic cannabinoids were reported by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) in a 2016 report, while 84 were reported to the National Forensic Laboratory Information System (NFLIS) in the United States in 2015. Synthetic cannabinoids have been implicated in an increasing number of emergency room admissions, death investigations, and high-profile intoxication events in corrections populations. Understanding the scale and scope of these events requires the availability of comprehensive analytical testing, which is currently lacking due to the speed with which new compounds appear. From a laboratory standpoint, the challenges of remaining current with synthetic cannabinoids stem from the diversity of compounds in the class; the large number of analogs, configurations, and isomer; and the delays in availability of analytical standards to confirm presence in biological samples. This proposal outlines a novel approach, where biological specimens and sample extracts (n=6,000) will be analyzed using a comprehensive non-targeted data acquisition method by high-resolution liquid chromatography time-of-flight mass spectrometry (LC-QTOF). This acquisition process will create a historical data archive that will be continually re-interrogated as new synthetic cannabinoids and their metabolites are discovered to determine retrospectively the date of first appearance and spread of new compounds as they appear on the drug market. This approach effectively allows us to comprehensively detect compounds today that are not incorporated into the defined scope of data analysis, and allows us to process that data using an expanded scope in the future without the need for retesting of sample. Using this approach will help increase the rate at which compounds not previously characterized and reported are identified, which will likely decrease the lag time between spikes in popularity and time of first detection. Our laboratory seeks to use this method and approach to study several different populations, including forensic toxicology of death investigation and human performance cases, workplace urine testing, and emergency medicine. Additional samples that may be included in this study include a military population of urine drug testing cases and a corrections population from the U.S. Federal Bureau of Prisons. This retrospective and comprehensive approach will allow for the ability to determine when new synthetic cannabinoids first appeared on the drug market, potential geographical distribution, and rates of synthetic cannabinoid use, despite the fact that targeted testing may not be available until months after initial appearance. Note: This project contains a research and/or development component, as defined in applicable law, and complies with Part 200 Uniform Requirements - 2 CFR 200.210(a)(14). ca/ncf