Tackling new psychoactive substances through metabolomics: UHPLC-HRMS study on natural and synthetic opioids in male and female murine models.

Novel psychoactive substances (NPS) represent a broad class of drugs new to the illicit market that often allow passing drug-screening tests. They are characterized by a variety of structures, rapid transience on the drug scene and mostly unknown metabolic profiles, thus creating an ever-changing scenario with evolving analytical targets. The present study aims at developing an indirect screening strategy for NPS monitoring, and specifically for new synthetic opioids (NSOs), based on assessing changes in endogenous urinary metabolite levels as a consequence of the systemic response following their intake. The experimental design involved in-vivo mice models: 16 animals of both sex received a single administration of morphine or fentanyl. Urine was collected before and after administration at different time points; the samples were then analysed with an untargeted metabolomics LC-HRMS workflow. According to our results, the intake of opioids resulted in an elevated energy demand, that was more pronounced on male animals, as evidenced by the increase in medium and long chain acylcarnitines levels. It was also shown that opioid administration disrupted the pathways related to catecholamines biosynthesis. The observed alterations were common to both morphine and fentanyl: this evidence indicate that they are not related to the chemical structure of the drug, but rather on the drug class. The proposed strategy may reinforce existing NPS screening approaches, by identifying indirect markers of drug assumption.

Pharmaco-toxicological effects of the novel tryptamine hallucinogen 5-MeO-MiPT on motor, sensorimotor, physiological, and cardiorespiratory parameters in mice-from a human poisoning case to the preclinical evidence.

RATIONALE: The 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT, known online as "Moxy") is a new psychedelic tryptamine first identified on Italian national territory in 2014. Its hallucinogen effects are broadly well-known; however, only few information is available regarding its pharmaco-toxicological effects. OBJECTIVES: Following the seizure of this new psychoactive substances by the Arm of Carabinieri and the occurrence of a human intoxication case, in the current study we had the aim to characterize the in vivo acute effects of systemic administration of 5-MeO-MiPT (0.01-30 mg/kg i.p.) on sensorimotor (visual, acoustic, and overall tactile) responses, thermoregulation, and stimulated motor activity (drag and accelerod test) in CD-1 male mice. We also evaluated variation on sensory gating (PPI, prepulse inhibition; 0.01-10 mg/kg i.p.) and on cardiorespiratory parameters (MouseOx and BP-2000; 30 mg/kg i.p.). Lastly, we investigated the in silico ADMET (absorption, distribution, metabolism, excretion, toxicity) profile of 5-MeO-MiPT compared to 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) and N,N-dimethyltryptamine (DMT). RESULTS: This study demonstrates that 5-MeO-MiPT dose-dependently inhibits sensorimotor and PPI responses and, at high doses, induces impairment of the stimulated motor activity and cardiorespiratory changes in mice. In silico prediction shows that the 5-MeO-MiPT toxicokinetic profile shares similarities with 5-MeO-DIPT and DMT and highlights a cytochrome risk associated with this compound. CONCLUSIONS: Consumption of 5-MeO-MiPT can affect the ability to perform activities and pose a risk to human health status, as the correspondence between the effects induced in mice and the symptoms occurred in the intoxication case suggests. However, our findings suggest that 5-MeO-MiPT should not be excluded from research in the psychiatric therapy field.

Oral fluid as a new investigative matrix for the determination of organic gunshot residue exposure.

In recent years, increased use of ammunition without lead and heavy metals was observed, leading to a growing interest in the detection of organic gunshot residues (OGSR) as evidence of firearms related crimes. The wide range of compounds belonging to the OGSR class hinders their mass spectrometric detection as different ionization techniques may be needed to obtain good results for all compounds. The purpose of this work was the development of a reliable analytical method by means of UHPLC-HRMS for the determination in oral fluid (OF) of the most common explosives and the most used stabilizers, arising from fire discharge and post-deflagration residues. For this purpose, SPE was used for OF clean-up before UHPLC-HRMS analysis. All target analytes were chromatographically separated by means of a Polar-C18 column. A chlorinated compound was added to the mobile phases in order to promote the formation of chloride adduct ions in the electrospray ion source operating in polarity switching to allow the best conditions for each analyte. The detection was conducted by means of a high-resolution mass spectrometer equipped with Orbitrap technology working in data dependent acquisition mode, in order to detect both the precursor ions and/or the most intense fragments for stabilizers. To verify its potential, the method was tested on real samples: a shooting session was performed in an open shooting range; the shooters fired from 2 to 20 rounds with a 9x21 caliber, thereafter OF was sampled. Samples were analyzed confirming that explosives may be detected in OF; the use of this matrix may be of great interest for investigative purposes as it is less affected by secondary transfer when compared to other commonly sampled matrices. The developed method could be a useful tool for law enforcement authorities for the detection of explosives in forensic potential scenarios, including biological matrices.

Simultaneous Quantification of 25 Fentanyl Derivatives and Metabolites in Oral Fluid by Means of Microextraction on Packed Sorbent and LC-HRMS/MS Analysis.

Fentanyl and fentalogs' intake as drugs of abuse is experiencing a great increase in recent years. For this reason, there are more and more cases in which it is important to recognize and quantify these molecules and related metabolites in biological matrices. Oral fluid (OF) is often used to find out if a subject has recently used a psychoactive substance and if, therefore, the person is still under the effect of psychotropics. Given its difficulty in handling, good sample preparation and the development of instrumental methods for analysis are essential. In this work, an analytical method is proposed for the simultaneous determination of 25 analytes, including fentanyl, several derivatives and metabolites. OF was collected by means of passive drool; sample pretreatment was developed in order to be fast, simple and possibly semi-automated by exploiting microextraction on packed sorbent (MEPS). The analysis was performed by means of LC-HRMS/MS obtaining good identification and quantification of all the analytes in less than 10 min. The proposed method was fully validated according to the Scientific Working Group for Forensic Toxicology (SWGTOX) international guidelines. Good results were obtained in terms of recoveries, matrix effect and sensitivity, showing that this method could represent a useful tool in forensic toxicology. The presented method was successfully applied to the analysis of proficiency test samples.

Seizures of New Psychoactive Substances on the Italian territory during the COVID-19 pandemic.

In recent years, the availability and the consequent consumption of New Psychoactive Substances (NPS) have proliferated at an unprecedented rate, posing a significant risk to the public health and challenging the law enforcement efforts to tackle the black market. In particular, large availability on Internet and unmonitored shipping have facilitated the diffusion of NPS on national territories. In this scenario, the forensic activity based on the process of drug detection, including investigation, seizure, recognition and analytical identification is crucial to get insights into the drug black market transformation. In this study, we describe the results obtained from the analysis of hundreds of packages seized during the months of year 2020, and suspected to contain NPS because not reacting with standard field test kits. We focused on the analysis by GC-MS and HPLC-HRMS, and NPS in particular, trying to underline the most common molecules present on the Italian territory during the COVID-19 pandemic. NPS were identified in 92.6% of the samples. The most prevalent compounds were synthetic cathinones, and 3-MMC in particular, which alone accounted for 18.6% of the total cases. Other prevalent molecules were 5F-MDMB-PICA, 2-FDCK, 1cp-LSD and 1P-LSD. Fentanyl was never detected. The information obtained from drug seizures is crucial to publish national alerts, which are in turn important to assist the legislative effort to ban new compounds and the update of toxicological and analytical methods.

Untargeted Metabolic Profiling of 4-Fluoro-Furanylfentanyl and Isobutyrylfentanyl in Mouse Hepatocytes and Urine by Means of LC-HRMS.

The diffusion of new psychoactive substances (NPS) is highly dynamic and the available substances change over time, resulting in forensic laboratories becoming highly engaged in NPS control. In order to manage NPS diffusion, efficient and innovative legal responses have been provided by several nations. Metabolic profiling is also part of the analytical fight against NPS, since it allows us to identify the biomarkers of drug intake which are needed for the development of suitable analytical methods in biological samples. We have recently reported the characterization of two new analogs of fentanyl, i.e., 4-fluoro-furanylfentanyl (4F-FUF) and isobutyrylfentanyl (iBF), which were found for the first time in Italy in 2019; 4F-FUF was identified for the first time in Europe and was notified to the European Early Warning System. The goal of this study was the characterization of the main metabolites of both drugs by in vitro and in vivo experiments. To this end, incubation with mouse hepatocytes and intraperitoneal administration to mice were carried out. Samples were analyzed by means of liquid chromatography-high resolution mass spectrometry (LC-HRMS), followed by untargeted data evaluation using Compound Discoverer software with a specific workflow, designed for the identification of the whole metabolic pattern, including unexpected metabolites. Twenty metabolites were putatively annotated for 4-FFUF, with the dihydrodiol derivative appearing as the most abundant, whereas 22 metabolites were found for iBF, which was mainly excreted as nor-isobutyrylfentanyl. N-dealkylation of 4-FFUF dihydrodiol and oxidation to carbonyl metabolites for iBF were also major biotransformations. Despite some differences, in general there was a good agreement between in vitro and in vivo samples.

Molecular Networking: A Useful Tool for the Identification of New Psychoactive Substances in Seizures by LC-HRMS.

New Psychoactive Substances (NPS) are a global concern since they are spreading at an unprecedented rate. Despite their commerce still being limited compared to traditional illicit drugs, the identification of NPS in seizures may represent a challenge because of the variety of possible structures. In this study we report the successful application of molecular networking (MN) to identify unexpected fentanyl analogs in two seizures. The samples were extracted with 1 mL of methanol and analyzed with an untargeted data-dependent acquisition approach by LC-HRMS. The obtained data were examined using the MN workflow within the Global Natural Product Search (GNPS). A job was submitted to GNPS by including both seizures and standard mixtures containing synthetic cannabinoids and fentanyls raw files; spectra obtained from standards were used to establish representative networks for both molecular classes. All synthetic cannabinoids in the mixture were linked together resulting in a molecular network despite their different fragmentation spectra. Looking at fentanyls, all the molecules with the typical 188.143 and 105.070 fragments were combined in a representative network. By exploiting the standard networks two unexpected fentanyls were found in the analyzed seizures and were putatively annotated as para-fluorofuranylfentanyl and (iso)butyrylfentanyl. The identity of these two fentanyl analogs was confirmed by NMR analysis. Other m/z ratios in the seizures were compatible with fentanyl derivatives; however, they appeared to be minor constituents, probably impurities or synthetic byproducts. The latter might be of interest for investigations of common fingerprints among different seizures.

Combination of pressurized liquid extraction with dispersive liquid liquid micro extraction for the determination of sixty drugs of abuse in hair.

The increasing phenomenon of drug addiction and the introduction of New Psychoactive Substances (NPS) have led to a progressive growth of research in the field of forensic analytical toxicology, with the need to develop modern and faster analytical procedures. Hair testing has gained increasing attention and recognition as a complement to blood and urine analysis, since it is a unique material for the retrospective detection of drugs, due to its large detection window. In this paper, a multiclass method for the simultaneous extraction, identification and quantification of sixty drugs of abuse belonging to different chemical classes in hair is proposed. This method can provide a valid, fast, simple and low-cost alternative to common tests; at the same time, it provides quantitative results, to concurrently confirm the assumption of one or more illicit substances. Both the decontamination step and the extraction of the analytes from the inner core of the hair were carried out by means of pressurized liquid extraction (PLE) while the clean-up was performed by dispersive liquid/liquid microextraction (dLLME), giving the great advantage of a high enrichment factor. The selected chromatographic conditions allowed a satisfying separation of the 60 analytes in 14 min, while the detection was conducted with a high-resolution mass spectrometer with Orbitrap technology. This multiclass method was suitable for analytes with different chemical characteristics allowing to reduce time and cost of analysis, organic solvent volume and the amount of sample required for analysis. The whole method was fully validated as confirmatory method following SWGTOX guidelines.

Neurological, sensorimotor and cardiorespiratory alterations induced by methoxetamine, ketamine and phencyclidine in mice.

Novel psychoactive substances are intoxicating compounds developed to mimic the effects of well-established drugs of abuse. They are not controlled by the United Nations drug convention and pose serious health concerns worldwide. Among them, the dissociative drug methoxetamine (MXE) is structurally similar to ketamine (KET) and phencyclidine (PCP) and was created to purposely mimic the psychotropic effects of its "parent" compounds. Recent animal studies show that MXE is able to stimulate the mesolimbic dopaminergic transmission and to induce KET-like discriminative and rewarding effects. In light of the renewed interest in KET and PCP analogs, we decided to deepen the investigation of MXE-induced effects by a battery of behavioral tests widely used in studies of "safety-pharmacology" for the preclinical characterization of new molecules. To this purpose, the acute effects of MXE on neurological and sensorimotor functions in mice, including visual, acoustic and tactile responses, thermal and mechanical pain, motor activity and acoustic startle reactivity were evaluated in comparisons with KET and PCP to better appreciate its specificity of action. Cardiorespiratory parameters and blood pressure were also monitored in awake and freely moving animals. Acute systemic administrations of MXE, KET and PCP (0.01-30 mg/kg i.p.) differentially alter neurological and sensorimotor functions in mice depending in a dose-dependent manner specific for each parameter examined. MXE and KET (1 and 30 mg/kg i.p.) and PCP (1 and 10 mg/kg i.p.) also affect significantly cardiorespiratory parameters, systolic and diastolic blood pressure in mice.

"Click and Screen" Technology for the Detection of Explosives on Human Hands by a Portable MicroNIR-Chemometrics Platform.

Portable near-infrared spectroscopy (MicroNIR) coupled with chemometrics was investigated for the first time as a new tool for the on-site analysis of explosives on human hands. A novel, entirely on-site approach based on the use of a particular miniaturized NIR spectrometer was developed and validated in cooperation with the Scientific Investigation Department (Carabinieri RIS) of Rome. Spectra from 25 volunteers were acquired in the NIR region in reflectance mode, and a prediction model was optimized on the basis of chemometric tools. The results demonstrated the capability of the MicroNIR-Chemometrics approach to correctly identify explosives from hands and not be affected by the complexity and variability of the matrix. This study has shown that the MicroNIR-Chemometrics approach can be considered a useful, fast, nondestructive tool identifying the manipulation of explosives in real forensic cases.

Identification of MT-45 Metabolites: In Silico Prediction, In Vitro Incubation with Rat Hepatocytes and In Vivo Confirmation.

MT-45 is a synthetic opioid with a pharmacological activity comparable to morphine and it has been involved in intoxications and fatalities reported in Europe and in USA. It was recently subject to control measures, but to date the metabolic pathways of the substance are still unknown. Using rat hepatocytes and LC-HRMS, 14 novel Phase I and II MT-45 metabolites were identified, products of monohydroxylation, dihydroxylation and N-dealkylation; glucuronide conjugation of mono- and dihydroxylated metabolites also occurred. The detected metabolites were firstly predicted in silico, then incubation of the drug with rat hepatocytes was carried out and the obtained metabolites were identified by LC-HRMS, with retention times, mass shift between theoretical mass and observed mass (<5 ppm), peak abundance and fragmentation pattern. Hydroxylated MT-45 was found to be the major metabolite of MT-45 in vitro experiments. The presence of all metabolites was confirmed by in vivo experiments in urine samples of CD-1 male mice; in these samples hydroxy-MT-45-glucuronide and di-hydroxy-MT-45-glucuronide are the most abundant metabolites, while the parent drug is found at concentration <10 ng mL-1 after 300 min. The knowledge of Phase I and II MT-45 metabolite structure is then crucial to develop analytical methods to identify MT-45 consumption in clinical and forensic testing.

Pharmaco-toxicological effects of the novel third-generation fluorinate synthetic cannabinoids, 5F-ADBINACA, AB-FUBINACA, and STS-135 in mice. In vitro and in vivo studies.

INTRODUCTION: 5F-ADBINACA, AB-FUBINACA, and STS-135 are 3 novel third-generation fluorinate synthetic cannabinoids that are illegally marketed as incense, herbal preparations, or research chemicals for their psychoactive cannabis-like effects. METHODS: The present study aims at investigating the in vitro and in vivo pharmacological activity of 5F-ADBINACA, AB-FUBINACA, and STS-135 in male CD-1 mice, comparing their in vivo effects with those caused by the administration of Δ9 -THC and JWH-018. In vitro competition binding experiments revealed a nanomolar affinity and potency of the 5F-ADBINACA, AB-FUBINACA, and STS-135 on mouse and human CB1 and CB2 receptors. Moreover, these synthetic cannabinoids induced neurotoxicity in murine neuro-2a cells. RESULTS: In vivo studies showed that 5F-ADBINACA, AB-FUBINACA, and STS-135 induced hypothermia; increased pain threshold to both noxious mechanical and thermal stimuli; caused catalepsy; reduced motor activity; impaired sensorimotor responses (visual, acoustic, and tactile); caused seizures, myoclonia, and hyperreflexia; and promoted aggressiveness in mice. Behavioral and neurological effects were fully prevented by the selective CB1 receptor antagonist/inverse agonist AM 251. Differently, the visual sensory response induced by STS-135 was only partly prevented by the AM 251, suggesting a CB1 -independent mechanism. CONCLUSIONS: For the first time, the present study demonstrates the pharmaco-toxicological effects induced by the administration of 5F-ADBINACA, AB-FUBINACA, and STS-135 in mice and suggests their possible detrimental effects on human health.

Cocaine profiling: Implementation of a predictive model by ATR-FTIR coupled with chemometrics in forensic chemistry.

In this study, a strategy based on Infrared Spectroscopy with Fourier Transformed and Attenuated Total Reflectance associated with chemometrics (ATR-FTIR) is proposed to identify the chemical "fingerprint" of cocaine samples. To this end, standard mixtures of cocaine and cuttings at differents ratio were investigated in order to develop a multivariate classification model to simultaneously predict the composition of the samples and to obtain a profile of adulteration of cocaine seizures. In addition, the application of a Partial Least Squares (PLS) and Principal Component Regression (PCR) calibration approaches were found to be a useful tool to predict the content of cocaine, caffeine, procaine, lidocaine and phenacetin in drug seizures. The achieved results on real confiscated samples, in cooperation with the Italian Scientific Investigation Department (Carabinieri-RIS) of Rome, allow to consider ATR-FTIR followed to chemometrics as a promising forensic tool in such situations involving profile comparisons and supporting forensic investigations.

Multi-class analysis of new psychoactive substances and metabolites in hair by pressurized liquid extraction coupled to HPLC-HRMS.

In this paper, an analytical method has been developed and validated for the analysis of new psychoactive substances (NPS) and metabolites in hair samples. The method was based on pressurized liquid extraction (PLE) followed by solid-phase extraction (SPE) clean-up and high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) analysis. To evaluate extraction efficiency and the applicability of the method, hair samples were fortified by soaking in order to obtain a good surrogate for drug users' hair; the amount of incorporated drugs related to their lipophilicity, similarly to in vivo drug incorporation. To the best of our knowledge, this is the first method that allowed for the analysis of both cathinones (5) and synthetic cannabinoids (7) in hair with a single extraction procedure and chromatographic run. A phenethylamine (2C-T-4), 4- fluorophenylpiperazine and methoxetamine were also included showing that PLE coupled to SPE clean-up was suitable for a multi-class analysis of NPS in hair. In addition, the use of PLE significantly reduced hair analysis time: decontamination, incubation, clean-up, and liquid chromatography-mass spectrometry (LC-MS) analysis were carried out in approximately 45 min. The method was fully validated according to Scientific Working Group for Forensic Toxicology (SWGTOX) and Society of Hair Testing (SoHT) guidelines. Limit of quantification (LOQ) values ranged from 8 to 50 pg mg-1 for cathinones, phenetylamines and piperazines, and from 9 to 40 pg mg-1 for synthetic cannabinoids (10 pg mg-1 for methoxetamine). Matrix effects were below 15% for all the analytes, demonstrating the effectiveness of the clean-up step. Inaccuracy was lower than 9% in terms of bias. Copyright © 2016 John Wiley & Sons, Ltd.

Purity and adulterant analysis of some recent drug seizures in Italy.

The data collected in this study describe an initial attempt to systematically introduce the qualitative and quantitative analysis of adulterants present in seized street drugs in Italy with the aim of improving surveillance and data sharing and for this purpose, the implementation of validated and standardized procedures are essential.

Effect of the novel synthetic cannabinoids AKB48 and 5F-AKB48 on "tetrad", sensorimotor, neurological and neurochemical responses in mice. In vitro and in vivo pharmacological studies.

RATIONALE: AKB48 and its fluorinate derivate 5F-AKB48 are two novel synthetic cannabinoids belonging to a structural class with an indazole core structure. They are marketed as incense, herbal preparations or chemical supply for their psychoactive Cannabis-like effects. OBJECTIVES: The present study was aimed at investigating the in vitro and in vivo pharmacological activity of AKB48 and 5F-AKB48 in male CD-1 mice and comparing their in vivo effects with those caused by the administration of Δ9-THC and JWH-018. RESULTS: In vitro competition binding experiments performed on mouse and human CB1 and CB2 receptors revealed a nanomolar affinity and potency of the AKB48 and 5F-AKB48. In vivo studies showed that AKB48 and 5F-AKB48, induced hypothermia, increased pain threshold to both noxious mechanical and thermal stimuli, caused catalepsy, reduced motor activity, impaired sensorimotor responses (visual, acoustic and tactile), caused seizures, myoclonia, hyperreflexia and promoted aggressiveness in mice. Moreover, microdialysis study in freely moving mice showed that systemic administration of AKB48 and 5F-AKB48 stimulated dopamine release in the nucleus accumbens. Behavioural, neurological and neurochemical effects were fully prevented by the selective CB1 receptor antagonist/inverse agonist AM 251. CONCLUSIONS: For the first time, the present study demonstrates the overall pharmacological effects induced by the administration of AKB48 and 5F-AKB48 in mice and suggests that the fluorination can increase the power and/or effectiveness of SCBs. Furthermore, this study outlines the potential detrimental effects of SCBs on human health.

Broad Screening and Identification of Novel Psychoactive Substances in Plasma by High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry and Post-run Library Matching.

Drug abuse is today a growing global problem. Often the consumers are not aware about the type of substances they are using and the correlated risks. In recent years, new psychoactive substances (NPS) appeared in the illicit market. The presence of NPS, such as synthetic cathinones, cannabinoids and phenethylamines, which are known to be pharmacologically and toxicologically hazardous, has been frequently reported. The aim of this study was the development of a liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method for a broad screening of NPS in plasma. Data acquisition was in MS/MS and full-scan modes and the method was validated for 25 NPS belonging to different chemical classes. Quantitative results have been obtained for these analytes with limits of quantification ranging from 0.03 to 0.4 ng/mL. The method was proven to be suitable for the screening of additional substances; to this aim, a post-run library matching was conducted for every sample with an in-house database containing over 300 NPS and known metabolites. The library may be constantly expanded with new drugs, in order to obtain a broad screening of NPS in biological matrices.

Pressurized liquid extraction for the determination of cannabinoids and metabolites in hair: Detection of cut-off values by high performance liquid chromatography-high resolution tandem mass spectrometry.

Hair analysis has become a routine procedure in most forensic laboratories since this alternative matrix presents clear advantages over classical matrices; particularly wider time window, non-invasive sampling and good stability of the analytes over time. There are, however, some major challenges for the analysis of cannabinoids in hair, mainly related to the low concentrations of 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol (THC-COOH), that is the major metabolite. In this study a fast, accurate and sensitive method for the determination of cannabinol, cannabidiol, THC and THC-COOH in hair has been developed. The extraction of analytes from hair (50mg) is based on an automated pressurized liquid extraction (PLE) using water modified with the surfactant sodium dodecyl sulphate as eluent phase. PLE extract is then cleaned up by SPE using polymeric reversed phase cartridges Strata XL before the injection in the HPLC-HRMS/MS system. Chromatographic conditions obtained with a fused-core column allowed a good separation of the analytes in less than 4min. The whole procedure has been validated according to SWGTOX guidelines. The LLOQs obtained for THC-COOH and the other analytes were respectively 0.1 and 2pg/mg. To the best of our knowledge, this is the first LC-MS/MS based method that allows the detection of THC-COOH in hair at values lower than the cut-off.

Micro-solid-phase extraction coupled to desorption electrospray ionization-high-resolution mass spectrometry for the analysis of explosives in soil.

Home-made micro-solid-phase extraction (SPE) cartridges using different adsorbent materials were tested for the desorption electrospray ionization-high-resolution mass spectrometry (DESI-HRMS) determination of explosives like 2,4,6-trinitrotoluene, cyclotrimethylene-trinitramine, cyclotetramethylene-tetranitramine, pentaerythritol tetranitrate, and trinitrophenylmethylnitramine in soil samples. Quantitation limits in the low nanogram per kilogram range proved the reliability of the method for the detection of explosives at ultra-trace levels. The reduced sample preparation allowed for low costs and high-throughput analyses. Finally, the superior extraction capability of the method was proved by obtaining DESI-HRMS responses at least five times higher than those achieved by performing DESI-HRMS analyses of solid-liquid extracts spotted onto commercial polytetrafluoroethylene slides.

Cavitand-based solid-phase microextraction coating for the selective detection of nitroaromatic explosives in air and soil.

A selective cavitand-based solid-phase microextraction coating was synthesized for the determination of nitroaromatic explosives and explosive taggants at trace levels in air and soil. A quinoxaline cavitand functionalized with a carboxylic group at the upper rim was used to enhance selectivity toward analytes containing nitro groups. The fibers were characterized in terms of film thickness, morphology, thermal stability, and pH resistance. An average coating thickness of 50 (±4) µm, a thermal stability until 400 °C, and an excellent fiber-to-fiber and batch to batch repeatability with RSD lower than 4% were obtained. The capabilities of the developed coating for the selective sampling of nitroaromatic explosives were proved achieving LOD values in the low ppbv and ng kg(-1) range, respectively, for air and soil samples.