Fragmentation pathways of odd- and even-electron N-alkylated synthetic cathinones

Abstract

Three ionization techniques, isotopic labeling, high-resolution mass spectrometry (HRMS) and multi-stage mass spectrometry (MSn) were used to analyze a series of N-alkylated synthetic cathinone derivatives and gain a deeper understanding of their fragmentation behavior during mass spectrometric analysis. The compounds analyzed represent 15 unique structures with common substitutions to the core synthetic cathinone structure, including substitutions to the aromatic ring and the number and types of N-alkyl functionalities. The analytical techniques employed include gas chromatography-electron ionization-mass spectrometry (GC-EI-MS), electrospray ionization-tandem mass spectrometry (ESI-MS/MS) with HRMS and direct analysis in real time tandem mass spectrometry (DART-MS/MS) with HRMS. These techniques cover a variety of forensic applications, including seized drug analysis, toxicological analysis and screening analysis, in local, state and federal laboratories. For collision-induced dissociation (CID) of protonated precursors, the spectra of 2° and 3° amines showed evidence for charge-remote and charge-directed fragmentation mechanisms. The 2° amines lost H2O as a dominant pathway whereas the 3° amines favored the formation of alkylphenones. As reported by others, CID of protonated N-alkylated cathinones containing 2° and 3°amines also provided an abundance of odd-electron product ions from the even-electron precursors. In contrast to the rearrangements observed in CID of protonated cathinones, EI fragmentation patterns were dominated by radical-directed cleavages to form iminium ions and charge-directed cleavages to form acylium ions. A comparison between the fragmentation behaviors of N-alkylated synthetic cathinones under all three ionization techniques enables a deeper understanding of N-alkylated synthetic cathinone fragmentation under varying instrumental setups.