Monitoring Changes in the Novel Psychoactive Substance (NPS) Market through Enhanced Identification of Emerging Drugs and their Metabolites in Biological Samples

As submitted by the applicant: Novel Psychoactive Substances (NPS) and research chemicals, abused for their euphoric and stimulating effects, have become widely circulated at electronic dance music festivals (EDM). Many of these products have been found to contain unregulated phenethylamines, cathinones, and synthetic cannabinoids. The range of NPS drugs currently available on the market has continued to grow due to their widespread availability over the internet and constant variation in product composition to circumvent changes in legislation. Building on analytical techniques, drug and metabolite libraries/databases, and operational deployment models developed under a prior round of NIJ funding (2013-DN-BX-K018), we propose anonymously collecting blood, urine and oral fluid from volunteer participants at three EDM festivals in the United States, including repeat visits to the Ultra Music Festival in Miami Florida. Collection at three different festivals will allow us to investigate regional differences in NPS use across the United States in populations where recreational drug use is high and many emerging NPS drugs are likely to be found. During the previous funding, we evaluated and ranked the effectiveness of six analytical approaches to NPS screening, and in the current proposal we will deploy the most effective of those methods to build on the drug and metabolite libraries/databases through the use of parent-metabolite linking, and in vitro confirmation of the identity of prominent biomarkers for purposes of improving approaches to forensic toxicological screening. Samples collected from participants will be screened for NPS drugs using gas chromatography- mass spectrometry (GC-MS) and Liquid Chromatography-Tandem Mass Spectrometry with High Resolution Time of Flight Mass Spectrometric Detection (LC-QTOF) in both targeted and non-targeted acquisition modes to increase the sensitivity and discriminating power over previously available platforms. Mass spectral databases created using the above approaches will be made available to publicly funded forensic laboratories, and findings will be rapidly disseminated through our website and presentations at professional meetings. The project will include additional studies to identify and characterize novel metabolites and degradation products of the most current NPS drugs using human liver microsome incubations and comparing the results of the in vitro predictions of metabolite targets with the authentic samples from the human subjects. As an additional benefit, identification of these metabolites will give insight to manufacturers of standard reference materials to improve the availability of commercial standards, allowing more laboratories to improve their testing procedures in both at- risk criminal justice and public health settings. This project contains a research and/or development component, as defined in applicable law. ca/ncf