Identification of two novel imidazole-derived GABA agonists butomidate and tf-etomidate in e-cigarette liquids

Recently, a number of abuse and intoxication cases involving imidazole-derived GABA agonists etomidate and its analogs have been reported in China. During our recent screening of e-cigarette liquids, we encountered two novel etomidate analogs that have not previously been reported. This study aims to present the analytical procedures used to identify these compounds, along with detailed data obtained under various instrumental conditions.

Identification of the substances of concern was carried out using various instruments, including gas chromatography-mass spectrometry (GC-MS), headspace gas chromatography (HS-GC), liquid chromatography-high-resolution mass spectrometry (LC-HRMS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Analysis of the e-cigarette samples of concern using GC-MS, LC-HRMS, and LC-MS/MS yielded mass spectra, product ion mass spectra, and high-resolution mass spectra, which allowed structural elucidation. HS-GC analysis of hydrolyzed alcohols provided further insights into the substituent groups linked to imidazole core. Finally, the compounds were identified as butomidate and trifluoro-etomidate (tf-etomidate) through comparison with reference standards. Product ion mass spectra of the reference standards at various collision energies were obtained by LC-MS/MS, which also matched those of the target compounds.

This study demonstrated the ion spectra of butomidate, sec-butomidate and tf-etomidate as obtained by GC-MS, and their product ion spectra under varying collision energies by LC-MS/MS. These findings enabled the identification of the compounds in the dubious e-cigarette liquids. To our knowledge, this is the first report detailing qualitative procedures and associated instrumental data for the identification of butomidate and tf-etomidate.