Toxicology in international drug control—Prioritizing the most harmful, persistent and prevalent substances

Ifeagwu, Susan C.; Raithelhuber, Martin; Crean, Conor; Gerostamoulos, Dimitri; Chung, Heesun; Tettey, J.N.A.

doi:10.1016/j.forsciint.2016.11.022

Cited by 12 publications

(5 citation statements)

References 4 publications

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“…3,4-Methylenedioxy-U-47700 (trans- N -2-(dimethylamino)cyclohexyl)- N -methylbenzo[d] [ 1 , 3 ] dioxole-5-carboxamide; Table 2 ) is the latest compound of this series to be reported to the EMCDDA EWS having been detected in a single sample seized in Poland in April 2018 [ 101 ]. The stereochemistry of the sample was not determined.…”

Section: The Appearance Of Non-fentanil Novel Synthetic Opioids On Ilmentioning

confidence: 99%

“…It is, therefore, necessary to take a risk assessment and harm reduction based approach to focus on those substances with the greatest prevalence and propensity for harm. Materials containing fentanyl and fentanils (fentanyl analogues) are considered by many the greatest concern due to their prevalence, potency and diversity [ 1 – 3 ]. There are also other non-fentanil novel synthetic opioids (NSOs) emerging across the illicit synthetic drug market, which adapt and diversify in a manner that is responsive to developments in the illicit drug supply chain and the new national and international legislation designed to disrupt them [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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The search for the “next” euphoric non-fentanil novel synthetic opioids on the illicit drugs market: current status and horizon scanning

et al. 2018

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PurposeA detailed review on the chemistry and pharmacology of non-fentanil novel synthetic opioid receptor agonists, particularly N-substituted benzamides and acetamides (known colloquially as U-drugs) and 4-aminocyclohexanols, developed at the Upjohn Company in the 1970s and 1980s is presented.MethodPeer-reviewed literature, patents, professional literature, data from international early warning systems and drug user fora discussion threads have been used to track their emergence as substances of abuse.ResultsIn terms of impact on drug markets, prevalence and harm, the most significant compound of this class to date has been U-47700 (trans-3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide), reported by users to give short-lasting euphoric effects and a desire to re-dose. Since U-47700 was internationally controlled in 2017, a range of related compounds with similar chemical structures, adapted from the original patented compounds, have appeared on the illicit drugs market. Interest in a structurally unrelated opioid developed by the Upjohn Company and now known as BDPC/bromadol appears to be increasing and should be closely monitored.ConclusionsInternational early warning systems are an essential part of tracking emerging psychoactive substances and allow responsive action to be taken to facilitate the gathering of relevant data for detailed risk assessments. Pre-emptive research on the most likely compounds to emerge next, so providing drug metabolism and pharmacokinetic data to ensure that new substances are detected early in toxicological samples is recommended. As these compounds are chiral compounds and stereochemistry has a large effect on their potency, it is recommended that detection methods consider the determination of configuration.

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Section: The Appearance Of Non-fentanil Novel Synthetic Opioids On Ilmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The search for the “next” euphoric non-fentanil novel synthetic opioids on the illicit drugs market: current status and horizon scanning

et al. 2018

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“…Due to their unknown origins, compositions, and lack of regulation, the use of these substances presents risks of harm, including toxicity, overdose, and death. , These risks may be exacerbated when a drug sample has an unknown quantity or is adulterated via the addition of other pharmaceutically active compounds to dilute, bulk up, or otherwise improve the appearance and/or apparent quality of the product. − Additional risk exacerbation occurs when a drug is mis-sold, e.g., counterfeited pharmaceuticals, , or when conventional illicit drugs, e.g., cocaine, MDMA, and ketamine, are adulterated with or substituted for structurally related analogues or novel psychoactive substances (NPS) such as synthetic cathinones, synthetic cannabinoids, or novel synthetic opioids such as fentanyl and its analogues . Due to their ever-increasing number and structural diversity (up to December 2020, 1047 NPS have been reported), the pharmacological properties of many NPS and their subsequent potential for adverse side effects are poorly understood. − Therefore, to provide effective public health and harm reduction interventions at large public events, there is a need for rapid qualitative and quantitative identification and characterization of the drug substances and combinations that are in use, including NPS that have not previously been reported or characterized. , Information regarding the presence and/or concentrations/amounts of these substances and assessment of their potential adverse effects can then be relayed to relevant stakeholders, such as first aid and medical personnel, peer-based harm reduction workers, and/or event patrons.…”

Section: Introductionmentioning

confidence: 99%

Early Warning System for Illicit Drug Use at Large Public Events: Trace Residue Analysis of Discarded Drug Packaging Samples

West

Fitzgerald

Hopkins

et al. 2021

J. Am. Soc. Mass Spectrom.

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Inspired by Locard's exchange principle, which states "every contact leaves a trace", a trace residue sampling strategy has been developed for the analysis of discarded drug packaging samples (DPS), as part of an early warning system for illicit drug use at large public events including music/dance festivals. Using direct analysis in real time/mass spectrometry and tandem mass spectrometry, rapid and high-throughput identification and characterization of a wide range of illicit drugs and adulterant substances was achieved, including in complex polydrug mixtures and at low relative ion abundances. A total of 1362 DPS were analyzed either off-site using laboratory-based instrumentation or on-site and in close to real time using a transportable mass spectrometer housed within a mobile analytical laboratory, with each analysis requiring less than 1 min per sample. Of the DPS analyzed, 92.2% yielded positive results for at least one of 15 different drugs and/or adulterants, including cocaine, MDMA, and ketamine, as well as numerous novel psychoactive substances (NPS). Also, 52.6% of positive DPS were found to contain polydrug mixtures, and a total of 42 different drug and polydrug combinations were observed throughout the study. For analyses performed on-site, reports to key stakeholders including event organizers, first aid and medical personnel, and peer-based harm reduction workers could be provided in as little as 5 min after sample collection. Following risk assessment of the potential harms associated with their use, drug advisories or alerts were then disseminated to event staff and patrons and subsequently to the general public when substances with particularly toxic properties were identified.

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“…With so many new potentially toxic substances emerging on the illicit market, analytical laboratories must make difficult decisions about which NPS to prioritize for the development of new assays. Generally, these decisions require individual scientists to consider and integrate multiple sources of information. , At the British Columbia Provincial Toxicology Centre (Vancouver, BC, Canada), for example, decisions about which reference materials to acquire are based on a compound’s reported national and international prevalence, its toxicity and forensic value, and clinician input. This information must be culled from a number of different sources, including the scientific literature, monographs, communications from public health agencies, and forensic databases, and then synthesized by experts in a subjective manner.…”

Section: Introductionmentioning

confidence: 99%

Identification of Emerging Novel Psychoactive Substances by Retrospective Analysis of Population-Scale Mass Spectrometry Data Sets

Skinnider,

Mérette,

Pasin

et al. 2023

Anal. Chem.

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Over the last two decades, hundreds of new psychoactive substances (NPSs), also known as "designer drugs", have emerged on the illicit drug market. The toxic and potentially fatal effects of these compounds oblige laboratories around the world to screen for NPS in seized materials and biological samples, commonly using high-resolution mass spectrometry. However, unambiguous identification of a NPS by mass spectrometry requires comparison to data from analytical reference materials, acquired on the same instrument. The sheer number of NPSs that are available on the illicit market, and the pace at which new compounds are introduced, means that forensic laboratories must make difficult decisions about which reference materials to acquire. Here, we asked whether retrospective suspect screening of population-scale mass spectrometry data could provide a data-driven platform to prioritize emerging NPSs for assay development. We curated a suspect database of precursor and diagnostic fragment ion masses for 83 emerging NPSs and used this database to retrospectively screen mass spectrometry data from 12,727 urine drug screens from one Canadian province. We developed integrative computational strategies to prioritize the most reliable identifications and tracked the frequency of these identifications over a 3 year study period between August 2019 and August 2022. The resulting data were used to guide the acquisition of new reference materials, which were in turn used to validate a subset of the retrospective identifications. Last, we took advantage of matching clinical reports for all 12,727 samples to systematically benchmark the accuracy of our retrospective data analysis approach. Our work opens up new avenues to enable the rapid detection of emerging illicit drugs through large-scale reanalysis of mass spectrometry data.

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Toxicology in international drug control—Prioritizing the most harmful, persistent and prevalent substances

Cited by 12 publications

References 4 publications

The search for the “next” euphoric non-fentanil novel synthetic opioids on the illicit drugs market: current status and horizon scanning

The search for the “next” euphoric non-fentanil novel synthetic opioids on the illicit drugs market: current status and horizon scanning

Early Warning System for Illicit Drug Use at Large Public Events: Trace Residue Analysis of Discarded Drug Packaging Samples

Identification of Emerging Novel Psychoactive Substances by Retrospective Analysis of Population-Scale Mass Spectrometry Data Sets

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