Development of an Analytical Method and Sample Preparation Technique for the Analysis of Sulfur-Containing Fentanyl Analogs by UPLCMSMS, and the Application to Forensic Science

In February 2018, the US DEA Agency released a statement of the emergency scheduling (Schedule 1) of all fentanyl analogs not already regulated by the CSA due to an alarming increase in overdose deaths linked to synthetic opioids. Fentanyl analogs are pharmacologically similar to fentanyl, but often more potent. This increased potency can create problems with proper dosing of fentanyl analogs leading to untoward effects including an increase in overdoses and deaths. Since 2018, there has been a 38.4% increase in illicitly manufactured fentanyl overdose deaths leading the CDC to make available the FAS Kit and Emergent Panels containing previously unavailable fentanyl analog reference materials. A limited number of published methods for the identification of multiple fentanyl analogs are available, none of which present a full analog class. Therefore, there is a need for analytical methods capable of identifying isomeric fentanyl analogs. Within the isomeric classes inter/intraclass isobars exist creating the issue of the same molecular weight and transitions, thus the mass spectrometer alone cannot identify the analogs. Given the increase in overdose deaths, an analytical method for identification and separation of all classes of fentanyl analogs is needed to help the clinical and forensic communities overcome this epidemic. Presented is a three-aim study including the development of a triple quadrupole mass spectral method, an ultra-pressure and high-performance liquid chromatographic method, and an extraction procedure capable of separation and detection of twelve sulfur-containing fentanyl analogs. Validation of the methods developed followed ANSI/SWGTOX guidelines including selectivity, carryover, precision, and LOD