Following regulatory controls on etomidate (October 2023) and its first-generation analogs (July 2024), novel analogs are rapidly emerging in China. Our laboratory has, for the first time, detected a novel analog in police-seized electronic cigarette liquids and in the hair of associated abusers — a substance that has not been documented in any prior scientific literature. The aim of this study was to describe the analytical procedures used to identify such compounds and to develop an high performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) assay for the simultaneous detection of eight analytes containing the novel analog and the metabolite etomidate acid in hair.

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

Analysis of the e-cigarette sample of concern using GC-MS and LC-HRMS yielded mass spectra, which allowed structural elucidation. HS-GC analysis of hydrolyzed alcohols provided further insights into the substituent groups linked to imidazole core, then the compound was identified as iso-butomidate through comparison with reference standards. The established HPLC-MS/MS method was validated and complied with international guidelines. Iso-butomidate was present in all five real hair samples (concentration range: 10.8–5,760pg/mg), whereas trifluoro-etomidate and etomidate were detected only in sample 5 (1,440 and 159pg/mg).

In this paper, a novel etomidate analog, iso-butomidate, was identified and an HPLC-MS/MS method was developed for the detection of eight imidazoles in hair and the method could be applied to authentic cases.