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The rise of fentanyl and fentanyl analogs in the drug supply pose serious threats to public health. Much of these compounds enter the United States through shipping routes. Here we provide a method for fentanyl screening and analysis that utilizes pressure‐sensitive adhesive (PSA) lined paper to recover drug residues from parcel‐related surfaces. The paper used is commercially available repositionable notes (also called post‐it or sticky notes). From this paper, mass spectra were obtained by paper spray‐mass spectrometry (PS‐MS), where PSA paper served as both a sampling and analysis substrate. Seven fentanyl‐related compounds were analyzed: fentanyl, 4‐anilino‐N‐phenethylpiperidine (4‐ANPP), N,1‐diphenethyl‐N‐phenylpiperidin‐4‐amine (phenethyl‐4‐ANPP), valerylfentanyl, 4‐fluoroisobutyrylfentanyl (4‐FIBF), carfentanil, and p‐fluorofentanyl. These compounds were recovered by PSA paper and identified by PS‐MS from packaging tape and plastic at 50 ng and from cardboard and shipping labels at 100 ng. The impact of cutting agents on PS‐MS analysis of fentanyl analogs was explored. No trends of analyte suppression were found at high concentrations of the cutting agents caffeine, diphenhydramine, and lidocaine when recovered from surfaces. A cartridge that required no precise cutting of PSA paper prior to sampling or analysis was evaluated for use in PS‐MS for fentanyl screening. Recovery and detection of fentanyl from plastic sheeting was demonstrated with this cut‐free cartridge. The cut‐free cartridge showed somewhat less consistency and lower analyte signal than the standard cartridge, but performance was suitable for potential screening applications. In combining PSA surface sampling with PS‐MS for drug screening, both sampling and detection of fentanyl‐related compounds is simple, rapid, and low‐cost. [ABSTRACT FROM AUTHOR]

Illicit drug trafficking and abuse is a significant public safety and health concern. Color tests are commonly used for drug screening, but their poor specificity results in false positives. This study demonstrates the combination of drug residue collection using pressure-sensitive adhesive paper, on-paper color testing, and post-reaction analysis by paper spray mass spectrometry (PS-MS) on both portable and benchtop ion trap MS. All steps, including residue collection, color testing, and paper spray analysis, were performed on the same piece of paper. Three common color tests were investigated: the cobalt thiocyanate test for cocaine, the Simon test for methamphetamine, and the Marquis test for phenethylamine stimulants and opiates. The detection threshold for color tests ranged from 1.25 to 10 μg on paper. Drug residues were successfully confirmed by paper spray MS at the color test threshold in all cases, except for heroin after reaction with the Marquis reagent, when using the portable MS. In this case, the MS detection threshold was 4-fold higher than the color test threshold. The stability of the color test products was assessed through a time study. Drug residues could be detected by MS at least 24 hours after reaction. A series of realistic samples, including false positives, were analyzed to demonstrate the technique's utility in real-world scenarios. Overall, combining color tests with PS-MS offers a rapid, low-cost method for the collection and analysis of illicit drugs. [ABSTRACT FROM AUTHOR]

Sulfur mustard (HD) poses a serious threat due to its relatively simple production process. Exposure to HD in the short-term causes an inflammatory response, while long-term exposure results in DNA and RNA damage. Respiratory tract tissue models were exposed to relatively low concentrations of HD and collected at 3 and 24 h post exposure. Histology, cytokine ELISAs, and mass spectrometric-based analyses were performed. Histology and ELISA data confirmed previously seen lung damage and inflammatory markers from HD exposure. The multi-omic mass spectrometry data showed variation in proteins and metabolites associated with increased inflammation, as well as DNA and RNA damage. HD exposure causes DNA and RNA damage that results in variation of proteins and metabolites that are associated with transcription, translation and cellular energy. [ABSTRACT FROM AUTHOR]

Despite the recent epidemic of fentanyl abuse, there are few validated assays capable of rapidly detecting these compounds. In order to improve the ability to detect carfentanil at physiologically relevant concentrations, we developed a systems biology approach to discover host-based markers which are specifically amplified upon exposure in a rabbit model. For this work, two "omics" pipelines utilizing mass spectrometry were developed and leveraged. First, a proteomics pipeline was developed to interrogate the blood plasma for protein-based biomarkers. Due to the incredible dynamic range of the plasma protein content, a multi-dimensional fractionation technique was used to partition and more accurately investigate the circulating plasma proteome. Isobaric tandem mass tags were integrated into the workflow to make quantitative assessments across all animals for an extended time course post-exposure. In addition to the proteomics efforts, blood plasma was also processed through an untargeted metabolomics pipeline. This approach allows for the identification of >800 small molecule features. By processing and analyzing data sets in parallel, we were able to identify a unique fingerprint of protein and metabolite perturbations that manifest following exposure to carfentanil. [ABSTRACT FROM AUTHOR]

Rationale: The analysis of chemical warfare agents (CWAs) from ambient atmosphere presents an analytical challenge due to their ease of degradation and volatility. Herein is described a method for derivatizing CWAs directly onto a paper spray substrate prior to analysis. This derivatization allows for much longer times of analysis without sample degradation and with little to no sample preparation. Methods: Derivatization was performed using 2‐[(dimethylamino)methyl] phenol both in‐vial and directly on paper spray cartridges. Solution studies were carried out over time and samples were analyzed via liquid chromatography/tandem mass spectrometry (LC/MS/MS) operated in positive ion mode. Paper spray substrates impregnated with the derivatizing agent prior to CWA vapor capture were also analyzed over time using a mass spectrometer operated in positive ion mode. Results: Use of 2‐[(dimethylamino)methyl] phenol as a paper spray substrate dopant enables derivatization of G‐series compounds into lower volatility complexes. The reaction occurs in solution and in the vapor phase. This new technique effectively traps and captures G‐series agents for analysis while extending the time for which the compound remains absorbed. The complex is highly suitable for direct analysis via paper spray mass spectrometry. Conclusions: Derivatization of paper spray substrates was shown to greatly increase the time for analysis of CWAs. This technique, combined with the vapor phase capture stage outlined previously, allows for rapid, quantitative CWA detection by paper spray ionization with little or no sample preparation. [ABSTRACT FROM AUTHOR]

Yersinia pestis is a Gram negative zoonotic pathogen responsible for causing bubonic and pneumonic plague in humans. The pathogen uses a type III secretion system (T3SS) to deliver virulence factors directly from bacterium into host mammalian cells. The system contains a single ATPase, YscN, necessary for delivery of virulence factors. In this work, we show that deletion of the catalytic domain of the yscN gene in Y. pestis CO92 attenuated the strain over three million-fold in the Swiss-Webster mouse model of bubonic plague. The result validates the YscN protein as a therapeutic target for plague. The catalytic domain of the YscN protein was made using recombinant methods and its ATPase activity was characterized in vitro. To identify candidate therapeutics, we tested computationally selected small molecules for inhibition of YscN ATPase activity. The best inhibitors had measured IC50 values below 20 μM in an in vitro ATPase assay and were also found to inhibit the homologous BsaS protein from Burkholderia mallei animal-like T3SS at similar concentrations. Moreover, the compounds fully inhibited YopE secretion by attenuated Y. pestis in a bacterial cell culture and mammalian cells at μM concentrations. The data demonstrate the feasibility of targeting and inhibiting a critical protein transport ATPase of a bacterial virulence system. It is likely the same strategy could be applied to many other common human pathogens using type III secretion system, including enteropathogenic E. coli, Shigella flexneri, Salmonella typhimurium, and Burkholderia mallei/pseudomallei species. [ABSTRACT FROM AUTHOR]

In Escherichia coli, PhoR is the histidine kinase of the phosphate regulon. It has been postulated that PhoR may function as a phospho-PhoB phosphatase. Experiments with four precise phoR deletion mutants supported this hypothesis and suggested that this activity resides within the histidine phosphorylation domain. This biochemical activity was confirmed by using a separately expressed histidine phosphorylation domain. [ABSTRACT FROM AUTHOR]

The cover image is based on the Research Article On‐Substrate Derivatization for Highly Volatile G‐Series Chemical Warfare Agent Detection via Paper Spray Mass Spectrometry by Phillip M. Mach et al., https://doi.org/10.1002/rcm.8276. [ABSTRACT FROM AUTHOR]

Paper spray ionization has grown to become one of the most successful ambient ionization methods within the past decade. Requiring little to no sample preparation and being remarkably simple to construct, this technique has seen application in a wide number of fields. This review approaches the mechanism of how paper spray works, and seeks to better classify what it is and is not in a rapidly expanding field of ambient techniques. Additionally, many applications of the technique in clinical, forensic, environmental, and reaction monitoring regimes are explored. Finally, perspectives towards the future of how paper spray could be utilized will be expanded upon, including unexplored substrates and possibilities for the 'omics space. Image 1 • Paper spray has become one of the most popular ambient ionization techniques. • Significant progress has been made recently in developing methods and applications. • Herein these methods and applications are explored in a variety of research spaces. • Future efforts will include 'omics applications and further design developments. [ABSTRACT FROM AUTHOR]

Paper spray mass spectrometry has been shown to successfully analyze chemical warfare agent (CWA) simulants. However, due to the volatility differences between the simulants and real G-series (i.e., sarin, soman) CWAs, analysis from an untreated paper substrate proved difficult. To extend the analytical lifetime of these G-agents, metal-organic frameworks (MOFs) were successfully integrated onto the paper spray substrates to increase adsorption and desorption. In this study, several MOFs and nanoparticles were tested to extend the analytical lifetimes of sarin, soman, and cyclosarin on paper spray substrates. It was found that the addition of either UiO-66 or HKUST-1 to the paper substrate increased the analytical lifetime of the G-agents from less than 5 min detectability to at least 50 min.