Direct analysis by ultra-high-resolution mass spectrometry of lipid A and phospholipids from Acinetobacter baumannii cells.

Acinetobacter baumannii, classified as priority number one by the World Health Organization (WHO), is an opportunistic pathogen responsible for infection and is able to develop antibiotic resistance easily. Membranes are bacteria's first line of defense against external aggression, such as antibiotics. A chemical modification of a lipid family or a change in lipid composition can lead to resistance to antibiotics. In this work, we analyzed different A. baumannii strains from various environments with different antibiotic resistance profiles, using matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FT-ICR MS). This study shows that it is possible to describe the main lipidome (phospholipids and lipid A) from the simple preparation of lysed cells, and that despite the complexity of the mixture. This ultra-high resolution mass spectrometry technique enables the separation of isobaric ion, to report a new class of lipids. Given its performance, this technique can be used to quickly and reliably characterize the lipidome of clinical strains from different environments.

Characterization of cigarette smokeomics by in situ solid-phase microextraction and confined-space direct analysis in real time mass spectrometry.

Characterization of chemical composition in cigarette smoke is essential for establishing smoke-related exposure estimates. Currently used methods require complex sample preparation with limited capability for obtaining accurate chemical information. We have developed an in situ solid-phase microextraction (SPME) method for online processing of smoke aerosols and directly coupling the SPME probes with confined-space direct analysis in real time (cDART) ion source for high-resolution mass spectrometry (MS) analysis. In a confined space, the substances from SPME probes can be efficiently desorbed and ionized using the DART ion source, and the diffusion and evaporation of volatile species into the open air can be largely avoided. Using SPME-cDART-MS, mainstream smoke (MSS) and side-stream smoke (SSS) can be investigated and the whole analytical protocol can be accomplished in a few min. More than five hundred substances and several classes of compounds were detected and identified. The relative contents of 13 tobacco alkaloids were compared between MSS and SSS. Multivariate data analysis unveiled differences between different types of cigarette smoke and also discovered the characteristic ions. The method is reliable with good reproducibility and repeatability, and has the potential to be quantitative. This study provides a simple and high-efficiency method for smokeomics profiling of complex aerosol samples with in situ online extraction of volatile samples, and direct integration of extracted probes with a modified ambient ionization technique.

Interlaboratory and cross-platform accessibility of time-of-flight wood identification database.

The mass spectral database of tree species built by US Fish and Wildlife Service has thousands of entries and has been a valuable resource to combat illegal logging and international trade. The database was and continues to be constructed using a particular ambient ionization time-of-flight mass spectrometry (TOF-MS) platform in the agency branch in Ashland, OR, with which queries of unknown wood samples are investigated exclusively. Laboratories that operate different MS instruments also have an interest in using the database if they can produce valid matches to known samples compatible with the database. Four species were selected for inter-laboratory comparison using Orbitrap MS instruments and the equivalent TOF-MS platform with direct analysis in real time ionization of institution-sourced wood samples. Identities of the known samples were confirmed by examination of their microscopic wood anatomy. Orbitrap analysis was able to identify each species as confidently as the TOF instruments, often with less variation in spectra but not necessarily greater mass accuracy or better-matched signal abundance to the control database. The Orbitrap program also had to be doubled to two scanned mass ranges appended for greater peak intensity, before spectra could be correctly matched to the database, but the program was successful.

Rapid analysis of untreated food samples by gel loading tip spray ionization mass spectrometry.

Rapid, efficient, versatile, easy-to-use, and non-expensive analytical approaches are globally demanded for food analysis. Many ambient ionization approaches based on electrospray ionization (ESI) have been developed recently for the rapid molecular characterization of food products. However, those approaches mainly suffer from insufficient signal duration for comprehensive chemical characterization by tandem MS analysis. Here, a commercially available disposable gel loading tip is used as a low-cost emitter for the direct ionization of untreated food samples. The most important advantages of our approach include high stability, and durability of the signal (> 10 min), low cost (ca. 0.1 USD per run), low sample and solvent consumption, prevention of tip clogging and discharge, operational simplicity, and potential for automation. Quantitative analysis of sulfapyridine, HMF (hydroxymethylfurfural), and chloramphenicol in real sample shows the limit-of-detection 0.1 µg mL-1, 0.005 µg mL-1, 0.01 µg mL-1; the linearity range 0.1-5 µg mL-1, 0.005-0.25 µg mL-1, 0.01-1 µg mL-1; and the linear fits R2 ≥ 0.980, 0.991, 0.986. Moreover, we show that tip-ESI can also afford sequential molecular ionization of untreated viscous samples, which is difficult to achieve by conventional ESI. We conclude that tip-ESI-MS is a versatile analytical approach for the rapid chemical analysis of untreated food samples.

A Snapshot, Using a Multi-Omic Approach, of the Metabolic Cross-Talk and the Dynamics of the Resident Microbiota in Ripening Cheese Inoculated with Listeria innocua.

Raw milk cheeses harbor complex microbial communities. Some of these microorganisms are technologically essential, but undesirable microorganisms can also be present. While most of the microbial dynamics and cross-talking studies involving interaction between food-derived bacteria have been carried out on agar plates in laboratory-controlled conditions, the present study evaluated the modulation of the resident microbiota and the changes of metabolite production directly in ripening raw milk cheese inoculated with Listeria innocua strains. Using a proxy of the pathogenic Listeria monocytogenes, we aimed to establish the key microbiota players and chemical signals that characterize Latteria raw milk cheese over 60 days of ripening time. The microbiota of both the control and Listeria-inoculated cheeses was analyzed using 16S rRNA targeted amplicon sequencing, while direct analysis in real time mass spectrometry (DART-HRMS) was applied to investigate the differences in the metabolic profiles of the cheeses. The diversity analysis showed the same microbial diversity trend in both the control cheese and the inoculated cheese, while the taxonomic analysis highlighted the most representative genera of bacteria in both the control and inoculated cheese: Lactobacillus and Streptococcus. On the other hand, the metabolic fingerprints revealed that the complex interactions between resident microbiota and L. innocua were governed by continuously changing chemical signals. Changes in the amounts of small organic acids, hydroxyl fatty acids, and antimicrobial compounds, including pyroglutamic acid, hydroxy-isocaproic acid, malic acid, phenyllactic acid, and lactic acid, were observed over time in the L. innocua-inoculated cheese. In cheese that was inoculated with L. innocua, Streptococcus was significantly correlated with the volatile compounds carboxylbenzaldheyde and cyclohexanecarboxylic acid, while Lactobacillus was positively correlated with some volatile and flavor compounds (cyclohexanecarboxylic acid, pyroxidal acid, aminobenzoic acid, and vanillic acid). Therefore, we determined the metabolic markers that characterize a raw milk cheese inoculated with L. innocua, the changes in these markers with the ripening time, and the positive correlation of flavor and volatile compounds with the resident microbiota. This multi-omics approach could suggest innovative food safety strategies based on the enhanced management of undesirable microorganisms by means of strain selection in raw matrices and the addition of specific antimicrobial metabolites to prevent the growth of undesirable microorganisms.

Recent advances in the application of direct analysis in real time-mass spectrometry (DART-MS) in food analysis.

Direct analysis in real time-mass spectrometry (DART-MS) has evolved as an effective analytical technique for the rapid and accurate analysis of food samples. The current advancements of DART-MS in food analysis are described in this paper. We discussed the DART principles, which include devices, ionization mechanisms, and parameter settings. Numerous applications of DART-MS in the fields of food and food products analysis published during 2018-2023 were reviewed, including contamination detection, food authentication and traceability, and specific analyte analysis in the food matrix. Furthermore, the challenges and limitations of DART-MS, such as matrix effect, isobaric component analysis, cost considerations and accessibility, and compound selectivity and identification, were discussed as well.

An Agile and Accurate Approach for N-Nitrosamines Detection and Quantification in Medicines by DART-MS.

N-nitrosamines (NAs) are prevalent mutagenic impurities in various consumer products. Their discovery in valsartan-containing medicines in 2018 prompted global regulatory agencies to set guidelines on their presence and permissible levels in pharmaceuticals. In order to determine the NAs content in medicines, efficient and sensitive analytical methods have been developed based on mass spectrometry techniques. Direct analysis in real time-mass spectrometry (DART-MS) has emerged as a prominent ambient ionization technique for pharmaceutical analysis due to its high-throughput capability, simplicity, and minimal sample preparation requirements. Thus, in this study DART-MS was evaluated for the screening and quantification of NAs in medicines. DART-MS analyses were conducted in positive ion mode, for both direct tablet analysis and solution analysis. The analytical performance was evaluated regarding linearity, precision, accuracy, limits of detection, and quantification. The DART-MS proved to be suitable for the determination of NAs in medicines, whether through direct tablet analysis or solution analysis. The analytical performance demonstrated linearity in the range from 1.00 to 200.00 ng mL-1, limits of quantification about 1.00 ng mL-1, precision and accuracy lower than 15%, and no significant matrix effect for six drug-related NAs. In conclusion, the DART-MS technique demonstrated to be an alternative method to determine NAs in medicines, aligning with the principles of green chemistry.

Ambient mass spectrometry imaging of food natural products by angled direct analysis in real time high-resolution mass spectrometry.

Direct surface analysis in ambient conditions provides information on the position and chemical composition of an object at the time of investigation. An angled sampling probe is developed in this work for direct analysis in real time (DART) ionization high-resolution mass spectrometry. The DART ion source and the interface were modified for improved surface resolution, increased ion transfer efficiency, as well as enabling two-dimensional surface scanning. The angled probe DART-MS system was used for investigating a variety of food samples including fruit peels, ginseng root, plant leaves and sections of radish. Abundant signals and distinct chemical profiles are obtained in seconds, and spatial distribution of different molecules across the sample surfaces can be observed. In addition, the developed system can quickly identify the chemical changes when the surfaces were treated. The method is capable of directly evaluating food sample surfaces with different shapes, hardness, and conditions, without any sample pretreatments.

A direct analysis method using sheath flow probe electrospray ionisation-mass spectrometry (sfPESI-MS) to detect drug residues from fingerprint forensic gel lifts.

Latent fingerprints at crime scenes are frequently recovered using forensic gel-lifters, which can help to preserve the crime scene and to enhance visualisation of traces such as blood or paint. In addition to providing fingerprint ridge detail, additional chemical information can also be recovered from gel lifts that may prove pertinent to an investigation. However, while DNA and metal ions have been shown to be able to be detected in gel-lifted fingerprints, the determination of other types of chemical information such as the presence of drugs in gel-lifted prints has not been previously shown. This study demonstrates the application of an ambient ionisation method, sheath flow probe electrospray ionisation-mass spectrometry (sfPESI-MS), to the direct analysis of gel-lifted fingerprints. A model drug compound (zolpidem) is successfully detected from gel-lifted prints from three different surface types: glass, metal, and paper. The surface activity-based separation associated with probe electrospray approaches is shown to resolve zolpidem ions from background phthalate species, significantly enhancing the response obtained from the gel-lifter. A depletion series experiment shows that the drug residue can be detected with up to 100% efficiency after eight consecutive contacts; however, detection efficiency drops to 20% after 30 contacts. The developed approach has potential application to analysis of historical gel-lifters to obtain additional chemical information.

Automatic MDSPE Combined with DART-HRMS for the Rapid Quantitation of 21 Synthetic Cathinones in Urine.

A new, rapid, and automated method for the quantitation of 21 synthetic cathinones in urine was established using magnetic dispersive solid-phase extraction (MDSPE) in combination with direct analysis in real time-high-resolution mass spectrometry (DART-HRMS). Sample preparation and quantitation were verified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methcathinone-D3, α-PVP-D8, and proadifen (SKF525A) were used as internal standards. Magnetic HLB extractant and NaH2PO4/NaOH buffer (0.2 M, pH 7) were used in automatic MDSPE. All 21 synthetic cathinones could be detected and analyzed by DART-HRMS in under 1 min. It was proven that the linearities of 21 synthetic cathinones were suitable (R2 > 0.99) in the concentration ranges of 0.5-100 ng/mL or 1-100 ng/mL. The precision and accuracy values were all within ±15%, and the samples were stable under various conditions. The average time of each sample from preprocessing to completion of detection was approximately 2 min, allowing for rapid sample analysis. The relative error (RE) of the concentrations obtained by DART-HRMS and LC-MS/MS were within ±13.61%, and the linear coefficient (R) was 0.9964. The results of DART-HRMS and LC-MS/MS provided equivalent values at the 95% confidence level. In summary, a simple, fast, and convenient quantitation method via DART-HRMS was established. This application can be utilized to reduce backlogs and promote rapid case processing.

Forensic analysis of biological fluid stains on substrates by spectroscopic approaches and chemometrics: A review.

BACKGROUND: Bodily fluid stains are one of the most relevant evidence that can be found at the crime scene as it provides a wealth of information to the investigators. They help to report on the individuals involved in the crime, to check alibis, or to determine the type of crime that has been committed. They appear as stains in different types of substrates, some of them porous, which can interfere in the analysis. The spectroscopy techniques combined with chemometrics are showing increasing potential for their use in the analysis of such samples due to them being fast, sensitive, and non-destructive. FINDINGS: This is a comprehensive review of the studies that used different spectroscopic techniques followed by chemometrics for analysing biological fluid stains on several surfaces, and under various conditions. It focuses on the bodily fluid stains and the most suitable spectroscopic techniques to study forensic scientific problems such as the substrate's characteristics, the influence of ambient conditions, the aging process of the bodily fluids, the presence of animal bodily fluids and non-biological fluids (interfering substances), and the bodily fluid mixtures. The most widely used techniques were Raman spectroscopy and attenuated total reflection Fourier transform infrared spectroscopy (ATR FTIR). Nonetheless, other non-destructive techniques have been also used, like near infrared hyperspectral imaging (HSI-NIR) or surface enhanced Raman spectroscopy (SERS), among others. This work provides the criteria for the selection of the most promising non-destructive techniques for the effective in situ detection of biological fluid stains at crime scene investigations. SIGNIFICANCE AND NOVELTY: The use of the proper spectroscopic and chemometric approaches on the crime scene is expected to improve the support of forensic sciences to criminal investigations. Evidence may be analysed in a non-destructive manner and kept intact for further analysis. They will also speed up forensic investigations by allowing the selection of relevant samples from occupational ones.

Chiral high-performance liquid chromatography analysis of mono-, di-, and triacylglycerols with amylose- and cellulose-phenylcarbamate-based stationary phases.

The ever-increasing technological advancement in the (ultra)high-performance liquid chromatography tandem (high-resolution) mass spectrometry platforms have largely contributed to steeply intensify the interest towards lipidomics research. However, mass spectrometers alone are unable to distinguish between enantiomers. This obstacle is especially evident in the case of glycerolipids analysis due the prochiral nature of glycerol. Until a couple of decades ago, the stereoselective analysis of triacylglycerols (TAGs) was performed on the end products generated either from their enzymatic or chemical hydrolysis, namely on mono- or diacyl-sn-glycerols (MAGs and DAGs, respectively). These were then mostly analyzed with Pirkle-type chiral stationary phases (CSPs) after dedicated multi-step derivatization procedures. One of the most significant drawbacks of these traditional methods for enantioselective TAGs analysis (actually of the produced MAGs and DAGs, often investigated as target species per se) was the difficulty to totally abolish the migration of fatty acyls between glycerol positions. This made difficult to control and keep unaltered the stereochemistry of the original molecules. Over the last two decades, it has been widely demonstrated that the enantioselective analysis of intact TAGs as well as of non-derivatized MAGs and DAGs can be efficiently obtained using polysaccharide-based CSPs incorporating either amylose- or cellulose-phenylcarbamate derivatives chiral selectors. In this paper, the enantioselective methods developed with these CSPs for the enantioselective direct LC analysis of MAGs, DAGs and TAGs embedding different types of fatty acid residues are comprehensively reviewed.

Surveillance of SARS-CoV-2, rotavirus, norovirus genogroup II, and human adenovirus in wastewater as an epidemiological tool to anticipate outbreaks of COVID-19 and acute gastroenteritis in a city without a wastewater treatment plant in the Peruvian Highlands.

The coronavirus disease 2019 (COVID-19) pandemic has demonstrated that Wastewater Based Epidemiology is a fast and economical alternative for monitoring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the community level in high-income countries. In the present study, wastewater from a city in the Peruvian Highlands, which lacks a wastewater treatment plant, was monitored for one year to assess the relationship between the concentration of SARS-CoV-2 and the reported cases of COVID-19 in the community. Additionally, we compared the relationship between rotavirus (RV), norovirus genogroup II (NoV GGII), and human adenovirus (HAdV) with the number of reported cases of acute gastroenteritis. Before commencing the analysis of the samples, the viral recovery efficacy of three processing methods was determined in spiked wastewater with SARS-CoV-2. This evaluation demonstrated the highest recovery rate with direct analysis (72.2 %), as compared to ultrafiltration (50.8 %) and skimmed milk flocculation (5.6 %). Wastewater monitoring revealed that 72 % (36/50) of the samples tested positive for SARS-CoV-2, with direct analysis yielding the highest detection frequency and quantification of SARS-CoV-2. Furthermore, a strong correlation was observed between the concentration of SARS-CoV-2 in wastewater and the reported cases of COVID-19, mainly when we shift the concentration of SARS-CoV-2 by two weeks, which allows us to anticipate the onset of the fourth and fifth waves of the pandemic in Peru up to two weeks in advance. All samples processed using the skimmed milk flocculation method tested positive and showed high concentrations of RV, NoV GGII, and HAdV. In fact, the highest RV concentrations were detected up to four weeks before outbreaks of acute gastroenteritis reported in children under four years of age. In conclusion, the results of this study suggest that periodic wastewater monitoring is an excellent epidemiological tool for surveillance and can anticipate outbreaks of infectious diseases, such as COVID-19, in low- and middle-income countries.

Plastic probe electrospray ionization mass spectrometry developed for rapid fingerprint profile of biological samples without pretreatment.

A triangular-shaped flat plastic substrate probe was prepared for direct electrospray ionization mass spectrometry (ESI-MS) for analysis of untreated chemical and biological samples including liquids (Met-Arg-Phe-Ala peptide, reserpine, and dodecyl aldehyde), solids (biological samples, traditional Chinese medicine), and powders (roasted coffee, rhizoma coptidis, lotus plumule, and Schisandra sphenanthera). Quantitative analysis of reserpine in water yielded a detection limit of 1 ng mL-1, dynamic response range within 1-500 ng mL-1, and linearity of signal response ˃0.9925. Compared to the conventional capillary ESI, this plastic probe ESI offers lower cost of analysis (US $0.0056 per probe), higher sensitivity, lower sample consumption, longer signal duration (>6 min), better reproducibility, signal stability, and higher speed of analysis (<10 s per sample, including sample loading). Overall, the results indicate the potential of ESI-MS based on flat plastic probes as a versatile method for simple, sensitive, and stable analysis of untreated biological sample analysis.

Analysis of feed additives by DART mass spectrometry: method optimisation and applications for product traceability in the European Union focusing on coccidiostats and carotenoids.

In this study, direct analysis in real time high resolution mass spectrometry (DART-HRMS) was used to investigate the accurate characterisation of feed additive formulations containing coccidiostats or carotenoids. The study demonstrates the efficacy of DART-HRMS in identifying the active substances in these formulations and distinguishing between feed additives with the same active substance. The protocol for this method involves two simple steps that are extracting samples with organic solvents and measuring the extracts with DART-HRMS. The study also employs various statistical tools, including a factorial design approach, to optimise the DART-HRMS settings, and multivariate statistics, to establish classification models for feed additive formulations using nominal mass spectra. Our study demonstrates the potential of DART-HRMS in ensuring the correct identification of feed additives containing various coccidiostats or carotenoids and proposes this tool as an additional means for compliance checks with EU regulations.

Recent application of direct analysis in real time mass spectrometry in plant materials analysis with emphasis on traditional Chinese herbal medicine.

Direct analysis in real time (DART) represents a new generation of ionization techniques that are used to rapidly ionize small molecules under ambient environments. The combination of DART with various mass spectrometry (MS) instruments allows analyzing multiple plant materials, including traditional Chinese herbal medicines (TCHMs), under simple or no sample treatment conditions. This review discussed the DART principles, including devices, ionization mechanisms, and operation parameters. Typical spectra detected by DART-MS were exhibited and discussed. Numerous applications of DART-MS in the fields of plant material and TCHM analysis were reviewed, including compound identification, biomarker discovery, fingerprinting analysis, and quantification analysis. Besides, modifications and improvements of DART-MS, such as hyphenated application with other separation methods, laser-based desorption techniques, and online sampling configuration, were summarized as well.

Direct multi-elemental analysis of cerebrospinal fluid samples by LA-ICP-MS employing an aerosol local extraction cryogenic ablation cell.

A novel method for direct high-throughput analysis of multi-elements in cerebrospinal fluid (CSF) samples by laser ablation inductively coupled plasma mass spectrometry with an aerosol local extraction cryogenic ablation cell (ALEC-LA-ICP-MS) was developed. Microliter-level CSF samples were frozen by a designed cryogenic ablation cell and directly analyzed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) without time-consuming pretreatment. Compared with the precision obtained at room temperature (20℃), that obtained at low temperature (- 25℃) was significantly improved; the RSDs were reduced from 8.3% (Zn) to 32.6% (Mn) to 2.2% (Pb) to 6.5% (Mn) with six times parallel determination. To meet the analytical requirement of the micro-volume CSF samples, the laminar flow aerosol local extraction strategy was adopted to improve the transmission efficiency of aerosols, and the signal intensity was increased by four times compared with the standard commercial ablation cell. The standard solution with 0.4% bovine serum albumin (BSA) matrix was used as matrix-match external standard, and Rh was added into the samples as internal standard. The limits of detection (LODs) ranged from 0.17 µg·L-1 (Mn) to 8.67 µg·L-1 (Mg). Standard addition recovery experiments and the determination of CRM serum L-1 and L-2 were carried out to validate the accuracy of the method; all results indicated there were excellent accuracy and precision in the proposed method. The matrix-scanning function in the GeoLas software combined with the microwell plate realizes the high-throughput automatic analysis. Twenty-four CSF samples from different patients were determined; the results showed that there might be a correlation between the metal elements in CSF and the diseases, which means that the proposed method has potential in the diagnosis of neurological diseases.

Differentiation of Four Polyvinylidene Fluoride Polymers Based on Their End Groups by DART-FT-ICR MS and Kendrick Plots.

Nowadays, synthetic polymers are produced and used in many materials for different applications. Matrix-assisted laser desorption/ionization or electrospray mass spectrometry are classically used to investigate them, but these techniques require sample preparation steps, which are not always suitable for the study of insoluble or formulated polymers. Alternatively, direct real-time (DART) ionization analysis may be conducted without sample preparation. Four polyvinylidene fluoride (PVDF) polymers involving the C2H2F2 repeating unit coming from different suppliers have been analyzed by DART Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) in negative-ion mode. The obtained mass spectra systematically displayed an oligomeric distribution between m/z 400 and 1300 of [M - H]-, [M + O2]•-, and [M + NO2]- ions. Kendrick plots were used to ease the identification of PVDF end-groups and establish a difference between the samples. Both commercial PVDF polymers shared the same α+ω end groups formula, which confirmed a similar polymerization process for their synthesis. The two other PVDFs were clearly different from the commercial ones by the occurrence of specific end-groups. MS/MS and MS3 experiments were conducted to obtain structural information on these end-groups.

Pressure sensitive adhesives and paper spray-mass spectrometry for the collection and analysis of fentanyl-related compounds from shipping materials.

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.

On the challenge of unambiguous identification of fentanyl analogs: Exploring measurement diversity using standard reference mass spectral libraries.

Fentanyl analogs are a class of designer drugs that are particularly challenging to unambiguously identify due to the mass spectral and retention time similarities of unique compounds. In this paper, we use agglomerative hierarchical clustering to explore the measurement diversity of fentanyl analogs and better understand the challenge of unambiguous identifications using analytical techniques traditionally available to drug chemists. We consider four measurements in particular: gas chromatography retention indices, electron ionization mass spectra, electrospray ionization tandem mass spectra, and direct analysis in real time mass spectra. Our analysis demonstrates how simultaneously considering data from multiple measurement techniques increases the observable measurement diversity of fentanyl analogs, which can reduce identification ambiguity. This paper further supports the use of multiple analytical techniques to identify fentanyl analogs (among other substances), as is recommended by the Scientific Working Group for the Analysis of Seized Drugs (SWGDRUG).