New Age Therapeutics: Development and Validation of an Analytical Workflow for the Analysis of Psychedelics in Biological Matrices

Depression affects over 264 million individuals worldwide. Traditional treatment methods are often limited in scope and have significant drawbacks. Since 2018, noteworthy advancements in new age treatments, including medicinal applications of psychedelics, for treatment-resistant depression, have been made. These advances have propagated legislative initiatives and reform regarding psychedelic compounds previously denoted as Schedule I compounds with no accepted medical applications. Legislative changes including medical applications, decriminalization, and legalization of psychedelic compounds directly impact forensic toxicology laboratories nationwide. Given the analytical challenges associated with these compounds, forensic toxicology laboratories are left to develop and validate new analytical workflows for the identification and quantitation of psychedelic compounds for driving under the influence of drugs (DUID) and postmortem cases.  

The detection of psychedelic compounds including psilocybin and N,N-dimethyltryptamine (DMT) poses an analytical challenge in biological specimens due to their rapid metabolism and known structural instability. An analytical workflow for the identification and quantitation of these compounds and their main metabolites needs to consider appropriate long term storage conditions and sample preparation parameters to minimize the implications associated with their inherent instability. Additionally, the recent publications of ANSI/ASB Standard 113, Standard for Identification Criteria in Forensic Toxicology and ANSI/ASB Standard 098, Standard for Mass Spectral Analysis in Forensic Toxicology intensify the need for development and validation of an analytical workflow for psychedelic compounds that meets the requirements set forth in these national standards. 
The goal of this research project is to develop and validate an analytical workflow for the identification and quantitation of psychedelic compounds in whole blood and additional biological matrices using a combination of high-resolution mass spectrometry and LC-MS/MS in accordance with the ANSI/ASB Standard 036, Standard Practices for Method Validation in Forensic Toxicology. The objectives for the project are: 1) develop and validate an analytical workflow for psychedelic compounds in biological specimens including psilocybin/psilocin, DMT, and associated metabolites using high-resolution mass spectrometry for identification and LC-MS/MS for confirmation and quantitation; 2) investigate the stability of psychedelic compounds under long term storage conditions, during sample preparation, and as post sample preparation extracts; 3) investigate prevalence of psychedelic compounds utilizing the validated analytical workflow. This project has the potential to significantly impact the forensic science community by establishing a workflow for psychedelic compounds in biological specimens in accordance with ANSI/ASB standard requirements in addition to providing significant stability data enabling laboratories to make data driven decisions regarding these complex analytes. CA/NCF