Structural Characterization of Emerging Synthetic Drugs

This proposal addresses both the basic and applied needs of the forensic community focusing first to understand the fundamental behavior of drug fragmentation in mass spectrometers and then to inform practitioners about how to apply the knowledge to current and future casework. The identification of 'traditional' seized drugs like heroin and cocaine is readily accomplished by gas chromatography-mass spectrometry (GC-MS), but novel synthetic drugs present major challenges for both emergency room diagnoses and seized drug analyses. In both areas, drug analysts may be faced with a mass spectrum that is not present in the database or cannot be explained by the analyst. One example is a major fragment ion of protonated synthetic cathinones; the fragment ion at m/z 91 is omnipresent in cathinone spectra, but the mechanism of formation has, to date, defied explanation. The goal of this proposal is to strengthen the reliability of forensic evidence by providing a more robust understanding of the interpretation of mass spectrometric data of two major classes of emerging synthetic drugs; cathinones and opioids. This proposal tackles a defined research need of the NIST OSAC subcommittee on Seized Drugs, which is "to develop an interpretation strategy that allows consistent conclusions to be drawn from [spectrometric] data." The mechanistic pathways of fragmentation will be elucidated through the synthesis and mass spectrometric analysis of isotopically-labeled drugs that will be synthesized by expert organic chemists on the collaborative team. Fragmentation mechanisms will be determined through beam-type collision-induced dissociation (CID), trap-type CID, and multiple levels of tandem mass spectrometry (MSn) to provide ultra-specific evidence of different pathways. The deliverables will also include comparisons and contrasts between the fragmentation mechanisms of odd-electron and even-electron ions, as formed by electron-ionization (El) and electrospray ionization (ESI), respectively. Our results will provide guidance to the forensic community about how to interpret the results of future analyses. The results will be presented at national forensic science conferences, published in peer-reviewed journals, and incorporated into GC-MS workshops that the Pl teaches to forensic practitioners. In addition to helping drug analysts identify emerging seized drugs, this project will inform medical professionals and policymakers about important public health decisions, like how to treat patients and how to identify illicit substances for future drug control. Spectra and data will be made publicly-available as supplemental data in the peer-reviewed literature and through archiving with NIJ. 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