Rapid Determination of Fentanyl-kind Analogs and Their Mass Fragmentation Routes by High Resolution Mass Spectrometry

To develop an approach of coupling liquid chromatography with Q-Exactive high resolution mass spectrometry (HRMS) for determination of 25 fentanyl-kind analogs and 2 precursors so that both the fragmentation pathways and characteristic ions of such fentanyl-kind analogs were to analyze for providing a reference into the identification of suspected fentanyl-kind chemicals without standards, meanwhile presenting a foundation for new psychoactive substances to be supervised timely or as early as possible. The fentanyl-kind solid drugs were extracted with methanol under ultrasound, and those liquid ones were extracted with acetonitrile via liquid-liquid extraction and salting-out procedures. The extracts were separated through a Hypersil GOLD C18 column (150mm×2.1mm×1.8μm) where a gradient elution was performed with a mobile phase consisting of methanol and water (2mmol/L ammonium acetate solution containing 0.1% formic acid). The fragmentation ions were acquired by HRMS in positive ion mode under full-scan-data-dependent MS2 (Full MS/dd-MS2). Finally, a mass-spectral library of 27 fentanyl-kind chemicals was thus established for qualitative analysis. 27 fentanyl-kind analogs were effectively separated along with the isomers. All the tested substances showed a low detection limit ranging among 0.05~2ng/mL and the quantitative limits for the solid-/liquid-form fentanyl-kind chemicals were 0.5μg/kg and 0.5ng/mL, respectively. Recoveries were all between 77.03% and 115.07%. Out from the ESI mode, the fentanyl-kind analogs mainly underwent McLafferty rearrangement (McL) through γ-hydrogen of piperidinyl ring being rearranged onto carbonyl oxygen and the carbonyl β-bond cleaved, hence having afforded the product ion (m/z 188). Hydrogen-transfer reaction resulted in the product ion to render a double bond which to ignite the further retro-Diels-Alder reaction of yielding the product ions (m/z160, 146, 134, 132). Dissociation of piperidinyl ring and phenylethyl formed the fragment ions at m/z 84, 105. The effort made here should be facilitating the identification of novel psychoactive substances with fentanyl as core (matrix) of the new synthetic chemicals, helpful to the qualitative and quantitative detection of seized chemical materials.