Underlying these societal challenges is a fundamental measurement issue-fentanyl analogs are difficult to unambiguously discriminate with analytical techniques typically found in forensic laboratories. For example, consider the near-identical centroided mass spectra of cyclopropyl fentanyl and crotonyl fentanyl, measured with electron ionization mass spectrometry (EI-MS), shown in Figure . Roughly speaking, in EI-MS, an analyte interacts with high energy electrons and forms ions. The relative abundance of these ions is then reported as a function of ion mass-to-charge ratio (m/z) in a data structure referred to as a mass spectrum. Because the m/z values depend only on the molecular constitution (viz., mass) of the observed ions, the mass spectra of isomeric compounds are often very similar. Spectral differences due to molecular connectivity will be reflected through changes in signal intensity that may be subtle or even indistinguishable (see Figure ). Due to difficulties with EI-MS, it is commonplace to leverage additional measurements, like chromatographic retention times, or other technologies altogether to help discriminate structurally similar compounds. Examples of these measurements include a bespoke gas chromatography (GC) mass spectrometry method for discriminating synthetic opioids , and ultra-high performance liquid chromatography tandem mass spectrometry method for discriminating between cyclopropyl fentanyl and crotonyl fentanyl in toxicology applications .