Detection of 4-FMC, 4-MeO-α-PVP, 4-F-α-PVP, and PV8 in blood in a forensic case using liquid chromatography–electrospray ionization linear ion trap mass spectrometry

Mochizuki, Akira; Adachi, Noboru; Shojo, Hideki

doi:10.1016/j.forsciint.2021.110888

Cited by 7 publications

(7 citation statements)

References 29 publications

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“…LC-MS/MS methods (electrospray ionization) is indeed an important alternative to overcome the GC limitations. The electrospray ionization is considered a soft technique, with little fragmentation of the molecule when compared to electron ionization used in GC-MS (Arantes et al, 2017;Mochizuki et al, 2021). Its multiple reaction monitoring (MRM) mode is ideal for quantitative methods, demonstrating Frontiers in Toxicology frontiersin.org high sensitivity (Poklis et al, 2016;Paul et al, 2017;Staeheli et al, 2017;Pieprzyca et al, 2018;Adamowicz et al, 2020a;Chan et al, 2021) compared to LC-MS and HPLC-DAD (Adamowicz et al, 2020b).…”

Section: Analytical Methods Applied In Toxicological Routine Analysismentioning

confidence: 99%

Fatal cases involving new psychoactive substances and trends in analytical techniques

et al. 2022

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New psychoactive substances (NPS) are an emerging public health issue and deaths are commonly associated with polydrug abuse. Moreover, the number of new substances available is constantly increasing, causing intoxications in low doses, characteristics that impose to toxicology and forensic laboratories to keep routine methods up to date, with high detectability and constantly acquiring new analytical standards. Likewise, NPS metabolites and respective elimination pathways are usually unknown, making it difficult the detection and confirmation of the drug involved in the fatal case in an analytical routine. A literature search was performed on PubMed, Scopus and Web of Science databases for papers related to chromatographic analyses from fatal cases related to NPS use published from 2016 to 2021. A total of 96 papers were retrieved and reviewed in this study. Opioids, synthetic cathinones, phenethylamines/amphetamines and cannabinoids were the NPS classes most found in the fatal cases. In many cases, multiple compounds were detected in the biological samples, including prescription and other illegal drugs. Liquid chromatography-tandem mass spectrometry, an alternative to overcome the gas chromatography–mass spectrometry limitations for some compounds, was the analytical technique most used in the studies, and high resolution mass spectrometry was often applied to NPS metabolite investigation and structural characterization and identification of unknown compounds. Toxicological screening and quantitation methods need to be continuously updated to include new substances that are emerging on the drug market that can be fatal at very low doses.

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Section: Analytical Methods Applied In Toxicological Routine Analysismentioning

confidence: 99%

Fatal cases involving new psychoactive substances and trends in analytical techniques

et al. 2022

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“…4F-α-PVP was also found in a multiple cathinone intoxication case at concentrations of 145 ng/mL in heart blood and 127 ng/mL in femoral vein blood. A 20-year-old male showed unusual behavior before his death and was found naked in his own room with his head through a wall [ 160 ]. Interestingly a case of diffuse alveolar hemorrhage following 4F-α-PVP and N -ethylpentedrone inhalation was also reported [ 161 ].…”

Section: Pharmacology and Toxicitymentioning

confidence: 99%

“…The concentrations found in cases of fatal PV8 intoxications were 70–260 ng/mL in blood and 110–130 ng/mL in urine (Table 1 ). PV8 was also determined in the liver and kidney, and autopsies showed pulmonary and cerebral edemata, and pathological changes in the heart [ 103 , 130 , 160 ]. Urinary concentrations of 2–1270 ng/mL were demonstrated in cases of non-fatal PV8 intoxications [ 159 ].…”

Section: Pharmacology and Toxicitymentioning

confidence: 99%

A review of synthetic cathinones emerging in recent years (2019–2022)

Kuropka¹,

Zawadzki

Szpot

2022

Forensic Toxicol

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Purpose The emergence of novel psychoactive substances (NPS) has been being a continuous and evolving problem for more than a decade. Every year, dozens of new, previously unknown drugs appear on the illegal market, posing a significant threat to the health and lives of their users. Synthetic cathinones are one of the most numerous and widespread groups among NPS. The purpose of this work was to identify and summarize available data on newly emerging cathinones in very recent years. Methods Various online databases such as PubMed, Google Scholar, but also databases of government agencies including those involved in early warning systems, were used in search of reports on the identification of newly emerging synthetic cathinones. In addition, threads on various forums created by users of these drugs were searched for reports on the effects of these new substances. Results We have identified 29 synthetic cathinones that have been detected for the first time from early 2019 to mid-2022. We described their structures, known intoxication symptoms, detected concentrations in biological material in poisoning cases, as well as the countries and dates of their first appearance. Due to the lack of studies on the properties of the novel compounds, we compared data on the pharmacological profiles of the better-known synthetic cathinones with available information on the newly emerged ones. Some of these new agents already posed a threat, as the first cases of poisonings, including fatal ones, have been reported. Conclusions Most of the newly developed synthetic cathinones can be seen as analogs and replacements for once-popular compounds that have been declining in popularity as a result of legislative efforts. Although it appears that some of the newly emerging cathinones are not widely used, they may become more popular in the future and could become a significant threat to health and life. Therefore, it is important to continue developing early warning systems and identifying new compounds so that their widespread can be prevented.

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“…In 2014, α-PVP was temporarily classified by the Drug Enforcement Administration (DEA) as a Schedule I compound [22], and since then new derivatives have emerged to replace it. Therefore, with the endeavor to identify and evaluate potential alternatives to α-PVP, as well as to study the structure-activity relationship (SAR) of halogen-substituted analogs of α-PVP, this study is focused on seven novel synthetic cathinones: 3-Fluoro-α-Pyrrolidinopentiophenone The use and abuse of para-halogenated α-PVP derivatives has already been reported [23][24][25][26][27][28][29]. In fact, 4-Cl-α-PVP was temporary classified as a Schedule I compound in 2019 [30].…”

Section: Introductionmentioning

confidence: 99%

“…Studies reported by [31,32] have demonstrated that para-halogenated α-pyrrolidinophenones act as potent DA uptake inhibitors. Regarding the in vivo effects, the authors of The use and abuse of para-halogenated α-PVP derivatives has already been reported [23][24][25][26][27][28][29]. In fact, 4-Cl-α-PVP was temporary classified as a Schedule I compound in 2019 [30].…”

Section: Introductionmentioning

confidence: 99%

Neuropsychopharmacology of Emerging Drugs of Abuse: meta- and para-Halogen-Ring-Substituted α-PVP (“flakka”) Derivatives

Nadal-Gratacós

Lleixà

Gibert-Serramià

et al. 2022

IJMS

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Changes in the molecular structure of synthetic cathinones has led to an increase in the number of novel emerging drugs in the illicit drug market at an unprecedented rate. Unfortunately, little is known about the neuropsychopharmacology of recently emerged halogen-substituted α-PVP derivatives. Thus, the aim of this study was to investigate the role of para- and meta-halogen (F-, Cl-, and Br-) substitutions on the in vitro, in silico, and in vivo effects of α-pyrrolidinopentiophenone (α-PVP) derivatives. HEK293 cells expressing the human dopamine or serotonin transporter (hDAT and hSERT) were used for the uptake inhibition and transporter affinity assays. Molecular docking was used to model the interaction mechanism against DAT. Swiss CD-1 mice were used for the horizontal locomotor activity, open field test, and conditioned place preference paradigm. All compounds demonstrated potent DA uptake inhibition and higher DAT selectivity than cocaine. Meta-substituted cathinones showed higher DAT/SERT ratios than their para- analogs, which correlates with an increased psychostimulant effect in vivo and with different meta- and para-in silico interactions at DAT. Moreover, all compounds induced rewarding and acute anxiogenic effects in mice. In conclusion, the present study demonstrates the role of meta- and para-halogen substitutions in the mechanism of action and provides the first evidence of the rewarding and anxiety-like properties of halogenated α-PVP derivatives.

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Detection of 4-FMC, 4-MeO-α-PVP, 4-F-α-PVP, and PV8 in blood in a forensic case using liquid chromatography–electrospray ionization linear ion trap mass spectrometry

Cited by 7 publications

References 29 publications

Fatal cases involving new psychoactive substances and trends in analytical techniques

Fatal cases involving new psychoactive substances and trends in analytical techniques

A review of synthetic cathinones emerging in recent years (2019–2022)

Neuropsychopharmacology of Emerging Drugs of Abuse: meta- and para-Halogen-Ring-Substituted α-PVP (“flakka”) Derivatives

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