scholarly journals Molecular Networking: A Useful Tool for the Identification of New Psychoactive Substances in Seizures by LC–HRMS

2020 ◽  
Vol 8 ◽  
Author(s):  
Flaminia Vincenti ◽  
Camilla Montesano ◽  
Francesca Di Ottavio ◽  
Adolfo Gregori ◽  
Dario Compagnone ◽  
...  

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.

2020 ◽  
Vol 10 (9) ◽  
pp. 606
Author(s):  
Liana Fattore ◽  
Matteo Marti ◽  
Rafaela Mostallino ◽  
Maria Paola Castelli

Sex and gender deeply affect the subjective effects and pharmaco-toxicological responses to drugs. Men are more likely than women to use almost all types of illicit drugs and to present to emergency departments for serious or fatal intoxications. However, women are just as likely as men to develop substance use disorders, and may be more susceptible to craving and relapse. Clinical and preclinical studies have shown important differences between males and females after administration of “classic” drugs of abuse (e.g., Δ9-tetrahydrocannabinol (THC), morphine, cocaine). This scenario has become enormously complicated in the last decade with the overbearing appearance of the new psychoactive substances (NPS) that have emerged as alternatives to regulated drugs. To date, more than 900 NPS have been identified, and can be catalogued in different pharmacological categories including synthetic cannabinoids, synthetic stimulants (cathinones and amphetamine-like), hallucinogenic phenethylamines, synthetic opioids (fentanyls and non-fentanyls), new benzodiazepines and dissociative anesthetics (i.e., methoxetamine and phencyclidine-derivatives). This work collects the little knowledge reached so far on the effects of NPS in male and female animal and human subjects, highlighting how much sex and gender differences in the effects of NPS has yet to be studied and understood.


Author(s):  
Olwen Groth ◽  
Simon Franz ◽  
Helena Fels ◽  
Julia Krueger ◽  
Gabriele Roider ◽  
...  

Abstract Purpose In forensics, entomological specimens can be used as additional/alternative matrices to detect xenobiotics when human specimens are limited in their application. Despite some advantages over implementing putrefied human remains, most medico-legal laboratories do not include entomotoxicological procedures as routine analytical methods. We thus applied two authentic cases to evaluate necrophagous larvae’s potential as complementary matrices for toxicological analysis after extensive postmortem decomposition. Methods Larvae and postmortem human samples, including hair, stomach contents, pericardial fluid, liver, lung, and skeletal muscle, were collected at autopsy. Samples were analyzed by liquid chromatography–tandem mass spectrometry and liquid chromatography–quadrupole time-of-flight mass spectrometry for pharmaceutical substances, illicit drugs, and new psychoactive substances, including synthetic cannabinoids, benzodiazepines, new synthetic opioids, and stimulants. Results Nearly all substances detected in human specimens, including several benzodiazepines and synthetic cannabinoids, were also detected in larvae. Surprisingly, some drugs, including the new psychoactive substances EAM-2201 and U-47700, were found exclusively in larvae and hair. The benzodiazepine etizolam was detected only in liver, lungs, and stomach contents, possibly resulting from characteristic tissue distribution in humans and/or larvae. Conclusions Antemortem external hair contamination with synthetic cannabinoids from side-stream smoke and postmortem hair contamination with substances in putrefaction fluids can be supposed in these cases. Our findings suggest that supplementary information can indeed be gained from analyzing larvae additional to those human specimens that are typically used for toxicological analysis after extensive postmortem decomposition. Nevertheless, these results represent merely two cases, requiring in-depth studies to determine whether such findings can identify acute intoxications as possible causes of death.


2018 ◽  
Vol 8 (9) ◽  
pp. 170 ◽  
Author(s):  
Paolo Frisoni ◽  
Erica Bacchio ◽  
Sabrine Bilel ◽  
Anna Talarico ◽  
Rosa Gaudio ◽  
...  

Background: New Psychoactive Substances (NPS) constitute a broad range of hundreds of natural and synthetic drugs, including synthetic opioids, synthetic cannabinoids, synthetic cathinones, and other NPS classes, which were not controlled from 1961 to 1971 by the United Nations drug control conventions. Among these, synthetic opioids represent a major threat to public health. Methods: A literature search was carried out using public databases (such as PubMed, Google Scholar, and Scopus) to survey fentanyl-, fentanyl analogs-, and other synthetic opioid-related deaths. Keywords including “fentanyl”, “fentanyl analogs”, “death”, “overdose”, “intoxication”, “synthetic opioids”, “Novel Psychoactive Substances”, “MT-45”, “AH-7921”, and “U-47700” were used for the inquiry. Results: From our literature examination, we inferred the frequent implication of fentanyls and synthetic opioids in side effects, which primarily affected the central nervous system and the cardiovascular and pulmonary systems. The data showed a great variety of substances and lethal concentrations. Multidrug-related deaths appeared very common, in most reported cases. Conclusions: The investigation of the contribution of novel synthetic opioid intoxication to death should be based on a multidisciplinary approach aimed at framing each case and directing the investigation towards targeted toxicological analyses.


Author(s):  
Maria Rosaria Varì ◽  
Giulio Mannocchi ◽  
Roberta Tittarelli ◽  
Laura Leondina Campanozzi ◽  
Giulio Nittari ◽  
...  

At the end of 2019, the European Monitoring Centre for Drugs and Drug Addiction was monitoring around 790 new psychoactive substances, more than twice the total number of controlled substances under the United Nations Conventions. These substances, which are not subject to international drug controls, include a wide range of molecules, including the assortment of drugs such as synthetic cannabinoids, stimulants, opiates, and benzodiazepines. Most of them are sold as “legal” substitutes for illicit drugs, while others are intended for small groups willing to experiment with them in order to know their possible new effects. At the national level, various measures have been taken to control new substances and many European countries have responded with specific legislation in favor of consumer safety and by extending or adapting existing drug laws to incorporate the new psychoactive substances. Moreover, since 1997, an early warning system has been created in Europe for identifying and responding quickly to the risks of new psychoactive substances. In order to establish a quicker and more effective system to address the criminal activities associated with new dangerous psychoactive substances, the European legal framework has considerably changed over the years.


2017 ◽  
Vol 41 (S1) ◽  
pp. S311-S311
Author(s):  
M. Lupi ◽  
T. Acciavatti ◽  
S. Marini ◽  
E. Cinosi ◽  
R. Santacroce ◽  
...  

IntroductionComorbidities between psychiatric diseases and consumption of traditional substances of abuse are common. Nevertheless, there is no data regarding the use of novel psychoactive substances (NPS) in the psychiatric population.ObjectivesThe purpose of this multicentre survey is to investigate the consumption of a wide variety of psychoactive substances in a young psychiatric sample.MethodsBetween September 2013 and November 2015, a questionnaire has been administered, in ten Italian psychiatric care facilities, to a sample of 671 psychiatric patients (48.5% men; 51.5% women), aged between 18 and 26 years (mean age: 22.24).Results8.2% of the sample declared use of NPS at least once in a lifetime and 2.2% have assumed NPS in the last three months. The NPS more used were synthetic cannabinoids (4.5%), followed by methamphetamine (3.6%). The three psychiatric diagnosis with more frequent NPS consumption were bipolar disorder (23.1%), personality disorders (11.8%) and schizophrenia and related disorders (11.6%). Bipolar disorder was associated with NPS consumption (P < .001). Among the illicit drugs investigated, 31.4% of the sample was cannabis smoker and 10.7% cocaine user. Moreover, 70.6% of the sample declared alcohol use and 47.7% had binge drinking conducts. In univariate regression analysis, bipolar disorder was positive associated with binge drinking while obsessive compulsive disorder resulted negative associated.ConclusionsThe use of novel psychoactive substances in a young psychiatric population appears to be a frequent phenomenon, probably still underestimated. Bipolar disorder shows an association with NPS use. Therefore, careful and constant monitoring and accurate evaluations of possible clinical effects related to their use are necessary.Disclosure of interestThe authors have not supplied their declaration of competing interest.


Author(s):  
Alex Stevens

This chapter analyses the development of British policy on illicit drugs from the late nineteenth century until 2016. It shows how this is characterized by contestation between social groups who have an interest in the control and regulation of some drugs and their users. It argues that there is a ‘medico-penal constellation’ of powerful organizations that produce British drug policy in accordance with their own ideas and interest. There have been clashes between the different principles held by people within these organizations but these have often been dealt with through the creation of pragmatic compromises. Recent examples include policies towards ‘recovery’ in drug treatment and new psychoactive substances whilst heroin-related deaths are used to explain why, so far, these pragmatic compromises have not ended the prohibition upon which British drug policy is based.


2020 ◽  
Vol 44 (7) ◽  
pp. 697-707
Author(s):  
Kelly Francisco da Cunha ◽  
Karina Diniz Oliveira ◽  
Marilyn A Huestis ◽  
Jose Luiz Costa

Abstract New psychoactive substances (NPS) are a major public health problem, primarily due to the increased number of acute poisoning cases. Detection of these substances is a challenge. The aim of this research was to develop and validate a sensitive screening method for 104 drugs of abuse, including synthetic cannabinoids, synthetic cathinones, fentanyl analogues, phenethylamines and other abused psychoactive compounds (i.e., THC, MDMA, LSD and their metabolites) in oral fluid by liquid chromatography–tandem mass spectrometry (LC–MS-MS). The Quantisal™ oral fluid device was used to collect oral fluid samples. The oral fluid–elution buffer mixture (500-μL sample) was extracted with t-butyl methyl ether, and chromatographic separation was performed on a Raptor™ biphenyl column (100 × 2.1 mm ID, 2.7 μm), with a total run time of 13.5 min. Limits of detection were established at three concentrations (0.05, 0.1 or 1 ng/mL) for most analytes, except for acetyl norfentanyl and mescaline (5 ng/mL). Matrix effects were generally &lt;20% and overall extraction recoveries &gt;60%. The highest matrix effect was observed within the synthetic cannabinoid group (PB22, −55.5%). Lower recoveries were observed for 2C-T (47.2%) and JWH-175 (58.7%). Recoveries from the Quantisal™ device were also evaluated for all analytes (56.7–127%), with lower recoveries noted for 25I-NBOMe, valerylfentanyl and mCPP (56.7, 63.0 and 69.9%, respectively). Drug stability in oral fluid was evaluated at 15, 60 and 90 days and at 25, 4 and −20°C. As expected, greater stability was observed when samples were stored at −20°C, but even when frozen, some NPS (e.g., synthetic cannabinoids) showed more than 20% degradation. The method was successfully applied to the analysis of seven authentic oral fluid samples positive for 17 different analytes. The method achieved good sensitivity and simultaneous detection of a wide range of NPS.


Bioanalysis ◽  
2020 ◽  
Vol 12 (21) ◽  
pp. 1557-1595
Author(s):  
Ana Y Simão ◽  
Mónica Antunes ◽  
Hernâni Marques ◽  
Tiago Rosado ◽  
Sofia Soares ◽  
...  

One of the problems associated with the consumption of new psychoactive substances is that in most scenarios of acute toxicity the possibility of quick clinical action may be impaired because many screening methods are not responsive to them, and laboratories are not able to keep pace with the appearance of new substances. For these reasons, developing and validating new analytical methods is mandatory in order to efficiently face those problems, allowing laboratories to be one step ahead. The goal of this work is to perform a critical review regarding bionalytical methods that can be used for the determination of new psychoactive substances (phenylethylamines, cathinones, synthetic cannabinoids, opioids, benzodiazepines, etc), particularly concerning sample preparation techniques and associated analytical methods.


2019 ◽  
Vol 16 (1) ◽  
pp. 97-113 ◽  
Author(s):  
Liviu Alexandrescu

Following the 2016 general ban on new psychoactive substances, synthetic cannabinoids (‘spice’-type drugs) have moved into unregulated street markets and have become popular among homeless populations in the United Kingdom. Images of so-called ‘spice zombies’, rough sleepers in public spaces experiencing severe substance-induced fits, have been used by local and national media to suggest the growing scale of the problem. This article proposes that such depictions should be read through a cultural analysis rooted in the political economy of austerity policies, where the twofold stigma of substance and welfare dependencies directs guilt at the poor, concealing the systemic cruelty of benefits reforms. Through the circulation of such tropes and the ridiculing of a superfluous abject underclass that embodies them, media and political discourses of the ‘broken society’ highlight an evident need for welfare reduction and more generally for the austerity project.


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