Development and validation of a combined selected ion monitoring-scan GC-EI-MS method for nitazene analogs

Novel synthetic opioids (NSOs) emerged during the third wave of the opioid epidemic, which has resulted in countless overdose deaths. Although fentanyl and fentanyl analogs are the most common NSOs, changing legislation in China and the United States led to the emergence of another class of NSOs, known as nitazene analogs. Nitazene analogs are very potent, and given their increasing prevalence in seized drug casework, it is imperative that seized drug laboratories have sufficient methods to identify nitazene analogs. This study developed a combined selected ion monitoring (SIM)-scan method to identify 20 nitazene analogs using gas chromatography-electron ionization-mass spectrometry (GC-EI-MS). The method was evaluated in terms of the limit of detection (LOD), carryover, selectivity, repeatability, reproducibility, and processed sample stability. The LOD for the targeted nitazene analogs ranged from 5 to 10 ppm due to increased sensitivity through SIM acquisition. No carryover was observed, and all nitazene analogs could be differentiated from other analogs and common interferences. The repeatability and reproducibility of the method were demonstrated qualitatively. All nitazene analogs were stable at room temperature for at least 24 hours. When applied to the analysis of blind simulant samples, 33 out of 35 samples were correctly identified, with the two misidentifications being due to ion ratios outside of tolerance. Likewise, two authentic nitazene analog casework samples were also correctly identified. The validated SIM-scan method provides a potential solution to identify low concentration nitazene analogs in seized drug casework that might otherwise be missed using routine GC-MS full scan acquisition.