Analysis of unknown fentanyl analogs using high resolution mass spectrometry with mass defect filtering

Drug overdoses in the United States have increased over the past several years due to the increase in the highly potent fentanyl and fentanyl analogs on the illicit drug market. Fentanyl analogs are created by altering the functional groups on the core fentanyl molecule. These molecules are continuously being tweaked which creates a challenge for forensic laboratories trying to identify these substances with traditional methods. Current screening methods of immunoassay or mass spectrometry target known standards for analysis and may not identify new analogs. Herein, we demonstrate a screening meth-odology that takes advantage of the mass accuracy afforded by a commercial high resolution mass spectrometer. A three-step, post-acquisition data analysis process identifies fentanyl analogs through mass defect filtering of unfragmented data, common fragments, and mass defect filtering of the frag-mented data. Using this method, analysts can identify potential fentanyl analog peaks in the spectra and can then perform further structural elucidation and identification.(c) 2022 Published by Elsevier B.V.