This study uses a combination of multi‐stage mass spectrometry (MSn), accurate mass measurements – with high‐resolution mass spectrometry (HRMS) – and isotopic labeling to characterize the fragmentation behavior of fentanyl and 4‐ANPP. By understanding the fragmentation behavior of fentanyl and its analogs in more detail, toxicologists and seized drug analysts will be better poised to identify new and emerging fentalogs, which are increasingly common and deadly adulterants in the growing opioid crisis. Throughout the literature the product ion at m/z 188 is often the most abundant fragment in the mass spectrometric analysis of fentanyl and fentanyl analogs, and this fragment is used for both qualitative and quantitative determinations. Our work shows there are at least three different structures for the isobaric fentanyl product ions at m/z 188, and they each form and fragment via different pathways. The development of fragmentation mechanisms to explain the observed fragmentation pathways of fentanyl and its main precursor 4‐ANPP helps contribute to the advancement of knowledge about fentanyl fragmentation and could provide important information for the identification of future fentanyl analogs.

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Fentanyl is a synthetic opioid that has been approved by the FDA as a general anesthetic because of its rapid onset and high potency. However, since 2013 an opioid epidemic involving fentanyl or fentanyl‐related compounds (FRCs) has swept the United States and caused numerous deaths in every state. The identification of novel FRCs is complicated by the rapid turnover of modifications to the core fentanyl structure. In this study, a series of 16 FRCs were analyzed using electrospray ionization tandem mass spectrometry (ESI‐MS/MS) to gain a deeper understanding of the conserved and unique fragmentation behaviors associated with substitution to the core fentanyl structure. This work provides an approach, based on the product ions from ESI‐MS/MS, to identify the modification site(s) on the core fentanyl structure for FRCs. Five common locations of substitution to the core fentanyl structure were used to assess the effect of substitution on the fragmentation behavior of FRCs. The proposed fragmentation pathways are supported through the combination of isotopic labeling, multi‐stage mass spectrometry (MSn), and accurate mass measurements with high‐resolution mass spectrometry (HRMS). The identification of primary product ions specific to regions of substitution provides an additional tool for the identification of the location of substitution to the core fentanyl structure, which ultimately will assist toxicologists and seized drug analysts in the identification of emerging FRCs.

The ability to detect atmospheric effluent from clandestine methamphetamine manufacture is a useful tool for law enforcement. A membrane inlet mass spectrometer is mounted onto an all-electric drive capable hybrid vehicle that samples the atmosphere while in motion. Attributing a latitude and longitude to each spectrum collected, unique chemical fingerprints from clandestine manufacture are then mapped. This location-based mass spectrum data provides a localization to an area of interest. The synthesis of methamphetamine precursors was performed, and the impurities from such reactions were observed. A mock manufacture was setup, and the impurities were introduced into the atmosphere via heating. The detection of products and impurities using this mobile platform has shown the effectiveness of locating and localizing the manufacture of methamphetamine.

Glycosaminoglycans (GAGs) participate in a broad range of physiological processes, and their structures are of interest to researchers in structural biology and medicine. Although they are abundant in tissues and extracellular matrices, their structural heterogeneity makes them challenging analytes. Mass spectrometry, and more specifically, tandem mass spectrometry, is particularly well suited for their analysis. Many tandem mass spectrometry techniques have been examined for their suitability toward the structural characterization of GAGs. Threshold activation methods such as collision-induced dissociation (CID) produce mainly glycosidic cleavages and do not yield a broad range of structurally informative cross-ring fragments. Considerable research efforts have been directed at finding other means of dissociating gas-phase GAG ions to produce more comprehensive structural information. Here, we compare the structural information on GAGs obtained by charge-transfer dissociation (CTD) and electron detachment dissociation (EDD). EDD has previously been applied to GAGs and is known to produce both glycosidic and cross-ring cleavages in similar abundance. CTD has not previously been used to analyze GAGs but has been shown to produce abundant cross-ring cleavages and no sulfate loss when applied to another class of sulfated carbohydrates like algal polysaccharides. In contrast to EDD, which is restricted to FTICR mass spectrometers, CTD can be implemented on other platforms, such as ion trap mass spectrometers (ITMS). Here, we show the capability of CTD-ITMS to produce structurally significant details of the sites of modification in both heparan sulfate (HS) and chondroitin sulfate (CS) standards ranging in length from degree of polymerization (dp) 4 to dp6. EDD and CTD both yield more structural information than CID and yield similar fractional abundances to one another for glycosidic fragments, cross-ring fragments, and neutral losses.