GC-MS By-product signatures enable reliable differentiation of isomeric synthetic cathinones

Synthetic cathinones are a prominent class of new psychoactive substances. The distinction between isomeric cathinones poses ongoing analytical challenges in forensic laboratories due to their almost indistinguishable electron ionization mass spectra at 70 eV (EIMS) and closely overlapping retention times under routine GC (gas chromatography) conditions. In this work, we demonstrate that the formation of thermally induced degradation products at the chromatographic inlet conditions, traditionally considered a serious analytical issue, can be systematically exploited to differentiate isomeric cathinones. As proof of principle, two series of isomeric cathinones were selected for analysis by gas chromatography-mass spectrometry (GC-MS): series A (nominal mass 235 Da), eutylone, pentylone, N-methylethylone, dibutylone, and series B (nominal mass 249 Da), dipentylone, N-ethylpentylone. The cathinones generated degradation products with a mass shift of -2 Da upon contact with the GC inlet at temperatures above 250 °C. Additionally, cathinones bearing a secondary amine substituent, i.e., eutylone, pentylone, and N-ethylpentylone, also produced by-products exhibiting a -4 Da mass shift. The EIMS spectra of the by-products showed characteristic fragmentation patterns, including diagnostic ions useful for differentiating the isomeric structures. Systematic evaluation of key parameters showed that by-product formation is mainly influenced by the GC injection mode (splitless rather than split) and elevated inlet temperatures (>250 °C). Analysis of real samples confirmed that the overall GC-MS by-product data enabled reliable characterization of cathinones. This work therefore reframes GC-MS as a source of structurally informative data and a simple, robust strategy for the forensic identification of isomeric cathinones.