Energy‐resolved mass spectrometry for differentiation of the fluorine substitution position on the phenyl ring of fluoromethcathinones

Abstract

A reliable method for structural analysis is crucial for the forensic investigation of new psychoactive substances (NPSs). Towards this end, mass spectrometry is one of the most efficient and facile methods for the identification of NPSs. However, the differentiation among 2-, 3-, and 4-fluoromethcathinones (o-, m-, and p-FMCs), which are ring-fluorinated positional isomers part of the major class of NPSs referred to as synthetic cathinones, remains a challenge. This is mostly due to their similar retention properties and nearly identical full scan mass spectra, which hinder their identification.

Discrimination and quantitation of halobenzoic acid positional isomers upon Th(iv) coordination by mass spectrometry

“…Ion mobility-MS is preferable for distinguishing large isomers with different shapes, sizes and collision cross sections such as peptides, 7 glycans, 8 lipids 9 and metabolites, 10 etc. Isomer discrimination by tandem MS is based on the gas-phase unimolecular fragmentation patterns 11–14 or reaction tendencies with metal ions, 15–17 which is applicable for small molecules. For the discrimination of XBA positional isomers, it is known that o -FBA (fluorobenzoic acid) is distinguishable from m -, p -FBA using solid-phase extraction coupled with ion chromatography–MS and o -CBA (chlorobenzoic acid) is distinguishable from m -, p -CBA using gas chromatography–MS due to the differences in retention time.…”

Regioisomer Differentiation of Ring-Substituted Chloromethcathinones and Bromomethcathinones Using Gas Chromatography/Electron Ionization-Triple Quadrupole Energy-Resolved Mass Spectrometry

“…Statistical calculations showed the considerable differences in the logarithmic values among the isomers (Tables S2 and S3). An analogous relationship was also previously established based on the measurement of the three FMC isomers ( ortho < para < meta ) . Such comprehensive assessments of the logarithmic values at various CEs enabled further unambiguous and reliable differentiation than the comparison of values only at a certain CE.…”

“…Dissociation energies for the CO elimination calculated from the free energies of the precursor and product molecules were determined to be in the following order: meta (68.5 kcal/mol) < para (73.8 kcal/mol) < ortho (75.8 kcal/mol) for CMCs and meta (67.8 kcal/mol) < para (73.3 kcal/mol) < ortho (74.6 kcal/mol) for BMCs, which were on the same order as those in the case of FMCs. 9 Therefore, the dissociation energy is significantly affected by the halogen substituent effects on the phenyl ring, possibly by the electron-donating resonance effect. This relationship of the dissociation energy can be used to establish the order of the CO elimination reactivity, ortho < para < meta, confirming the relationship determined by the ERMS evaluations.…”

“…Several research groups have developed spectrometric, spectroscopic, and multivariate analysis techniques for regioisomer differentiation of synthetic cathinones. − Herein, we used gas chromatography (GC)/electron ionization (EI)-triple quadrupole mass spectrometry (QqQ-MS). We have previously developed differentiation methods for ring-fluorinated regioisomers of synthetic cannabinoids and cathinones based on energy-resolved mass spectrometry (ERMS) using GC/EI-QqQ-MS. − In this application note, we extend this methodology to o -, m -, and p -CMCs together with m - and p -BMCs as analytes, and the viabilities of GC, full scan MS, and ERMS for the differentiation of positional isomers were investigated. To the best of our knowledge, this is the first report on discriminating positional isomers of ring-chlorinated and ring-brominated synthetic cathinones.…”

Retention Time and Optimal Collision Energy Advance Structural Annotation Relied on LC–MS/MS: An Application in Metabolite Identification of an Antidementia Agent Namely Echinacoside

“…Previously, energy-resolved MS was always accomplished by directly infusing authentic compound or multiply injecting sample with stepwise CEs, , and CE 50 was subsequently generated from a sigmoidal shaped breakdown graph. Herein, a robust method was proposed to achieve high throughput online energy-resolved MS for any fragment ion species-of-interest in a single analytical run, and the breakdown graphs of precursor-to-precursor ion pair and precursor-to-product ion transition are applied to generate CE 50 and OCE, respectively.…”