Structural Characterization of 4-Fluorometomidate: A Novel Metomidate Derivative Detected in an E-Cigarette.

The nonmedical use of etomidate and its structural analogs as additives in e-cigarettes has shown a significant growth trend, and the public health and safety risks arising from the abuse of such substances have drawn widespread attention. This study comprehensively employed gas chromatography-mass spectrometry, liquid chromatography-high-resolution mass spectrometry, and nuclear magnetic resonance spectroscopy (NMR) techniques to identify a novel metomidate analog, 4-fluorometomidate, in seized cartridges for the first time. Mass spectrometry analysis revealed that under electron ionization conditions, the compound produced fragment ions at m/z 77.1, 95.1, 103.1, 123.1, and 248.1. The molecular ion (m/z 248.1) and base peak (m/z 123.1) were both 18 Da higher than the corresponding peaks (m/z 230.1 and 105.1) characteristic for metomidate. In electrospray ionization mode, its protonated molecule (m/z 249.1032) also exhibited an increase of 17.9908 Da compared to metomidate (m/z 231.1124), and the characteristic fragment at m/z 123.0607 showed an increase of 17.9909 Da relative to the fragment of metomidate (m/z 105.0698), which was overall consistent with the substitution of one hydrogen atom by a fluorine atom (△m/z 17.9905). NMR analysis confirmed that the fluorine atom is located at the 4'-position of the benzene ring.