Identification and quantification of two etomidate analogues ABP-700 and 2,6-dichloro-3-fluoro-etomidate in e-cigarette liquid and hair by GC-MS and LC-MS/MS

Abstract

Purpose: In response to the Chinese government’s regulation of etomidate and some of its analogs, illicit manufacturers have turned to novel structural analogs of etomidate to circumvent legal restrictions. This study aims to establish a qualitative and quantitative ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the detection of two emerging etomidate analogs—ABP-700 and 2,6-dichloro-3-fluoro-etomidate—and apply it to the analysis of hair samples from actual abusers. Methods: Hair samples were washed, segmented, cryogenically ground, and extracted with methanol. For extraction, precisely 20 mg of homogenized hair sample was spiked with deuterated internal standard and subjected to methanol extraction with vortex mixing followed by centrifugation. The resulting supernatant was filtered through a 0.22 μm membrane filter prior to UPLC-MS/MS analysis. Results: The method showed excellent quantitative linearity (r² > 0.99) over the range of 0.01–1 ng/mg. The limits of detection and quantification were 0.005 ng/mg and 0.01 ng/mg for both analytes. In authentic hair samples from suspected abusers, ABP-700 was detected at 0.11 ng/mg and 0.02 ng/mg, while 2,6-dichloro-3-fluoro-etomidate was quantified at 0.13 ng/mg. Concentrations in seized e-cigarette liquids were 22.6 µg/mg and 48.6 µg/mg, respectively. Conclusions: This study establishes a validated analytical method for the simultaneous determination of ABP-700 and 2,6-dichloro-3-fluoro-etomidate in human hair matrices. To our knowledge, this is the first reported methodology enabling both identification and quantification of these novel etomidate analogs in hair samples, with successful application to forensic case samples.