Acrylfentanyl: Another new psychoactive drug with fatal consequences

Guerrieri, Davide; Rapp, Emma; Roman, Markus; Thelander, Gunilla; Kronstrand, Robert

doi:10.1016/j.forsciint.2017.05.010

Cited by 48 publications

(42 citation statements)

References 15 publications

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“…Recently, Sweden has seen a number of fentanyl analog-related fatalities that included substances such as acryl, furanyl and cyclopropyl fentanyl (EMCDDA 2018; Guerrieri et al 2017a, b). In particular, cyclopropyl fentanyl has been extensively used.…”

Section: Introductionmentioning

confidence: 99%

Correlations between metabolism and structural elements of the alicyclic fentanyl analogs cyclopropyl fentanyl, cyclobutyl fentanyl, cyclopentyl fentanyl, cyclohexyl fentanyl and 2,2,3,3-tetramethylcyclopropyl fentanyl studied by human hepatocytes and LC-QTOF-MS

et al. 2018

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Recently, a number of fentanyl analogs have been implicated in overdose deaths in Europe and in the US. So far, little is known of the molecular behavior of the structurally related subgroup; the alicyclic fentanyls. In this study, reference standards of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and 2,2,3,3-tetramethylcyclopropyl fentanyl (TMCPF) at a final concentration of 5 µM were incubated with cryopreserved human hepatocytes (1 × 106 cells/mL) for 0, 1, 3 and 5 h. The metabolites formed were identified by liquid chromatography–quadrupole time-of-flight mass spectrometry analysis. The most abundant biotransformation found was N-dealkylation (formation of normetabolites) and oxidation of the alicyclic rings. As ring size increased, the significance of N-dealkylation decreased in favor of alicyclic ring oxidation. An example of this was cyclopropyl fentanyl, with a three-carbon ring, whose normetabolite covered 82% of the total metabolic peak area and no oxidation of the alicyclic ring was observed. In contrast, TMCPF, with a seven-carbon ring structure, rendered as much as 85% of its metabolites oxidized on the alicyclic ring. Other biotransformations found included oxidation of the piperidine ethyl moiety and/or the phenethyl substructure, glucuronidation as well as amide hydrolysis to form metabolites identical to despropionyl fentanyl. Taken together, this study provides a base for understanding the metabolism of a number of structurally related fentanyl analogs formed upon intake.Electronic supplementary materialThe online version of this article (10.1007/s00204-018-2330-9) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Correlations between metabolism and structural elements of the alicyclic fentanyl analogs cyclopropyl fentanyl, cyclobutyl fentanyl, cyclopentyl fentanyl, cyclohexyl fentanyl and 2,2,3,3-tetramethylcyclopropyl fentanyl studied by human hepatocytes and LC-QTOF-MS

et al. 2018

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“…However, some NPS have been found particularly dangerous, due to high potency (eg, high receptor affinity) or severe side effects, requiring contact with poisons information centers and presentation at hospital emergency departments . The recent increasing use of highly potent NPS opioids, especially designer fentanyls, has caused many serious adverse events and overdose deaths linked to the well‐known side effects of decreased consciousness and respiratory depression …”

Section: Introductionmentioning

confidence: 99%

“…9,10 The recent increasing use of highly potent NPS opioids, especially designer fentanyls, has caused many serious adverse events and overdose deaths linked to the well-known side effects of decreased consciousness and respiratory depression. 5,[11][12][13][14][15][16][17] Drugs-of-abuse testing usually involves an initial, preliminary screening by immunoassays, after which any positive findings are subjected to confirmatory analysis by specific methods based on mass spectrometric (MS) detection. Due to the high turnover of NPS, upto-date commercial immunoassays for this type of drugs are rarely available, requiring direct use of more laborious and expensive MS methods for NPS testing.…”

mentioning

confidence: 99%

Detectability of fentanyl and designer fentanyls in urine by 3 commercial fentanyl immunoassays

Helander

Stojanović

Villén

et al. 2018

Drug Testing and Analysis

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In recent times, structural variants of fentanyl (designer fentanyls) have appeared on the recreational drug market for new psychoactive substances (NPS). These potent opioids have caused harmful intoxications and increased opioid-related mortality in many countries. This work evaluated 3 commercial immunoassays for fentanyl screening in urine and investigated whether they are useful also for screening of designer fentanyls. The assays examined were the Thermo DRI® Fentanyl Enzyme Immunoassay, the ARK™ Fentanyl Assay homogeneous enzyme immunoassay, and the Immunalysis® Fentanyl Urine SEFRIA™ Drug Screening Kit. A liquid chromatography-high-resolution mass spectrometry method was used as reference. The DRI fentanyl immunoassay generated somewhat higher assay imprecision values (%CV) compared with the ARK™ and SEFRIA™ assays, but all assays showed %CV values acceptable for routine use. The 3 assays showed overall good detectability (33%-95% cross-reactivity) for blank urine samples spiked with acetylfentanyl, acrylfentanyl, butyrfentanyl, 4-chloroisobutyrfentanyl, 4-fluorobutyrfentanyl, 4-fluorofentanyl, 4-fluoroisobutyrfentnyl, isobutyrfentanyl, methoxyacetylfentanyl, or tetrahydrofuranfentanyl, whereas 4-methoxybutyrfentanyl (all assays) and 2-fluorofentanyl (DRI assay) showed low cross-reactivity. A good detectability of designer fentanyls was confirmed in urine samples from authentic acute intoxications. In conclusion, the present results demonstrate that the urinary fentanyl immunoassays are generally useful also for preliminary screening of fentanyl analogs sold as NPS. When the SEFRIA™ assay was applied for testing of 980 urine samples from patients treated for drug dependence in Sweden, only 1 sample was confirmed positive for fentanyl.

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“…6 Because fentanyl and its analogs are highly potent, doses as small as 1 mg can be lethal. 7,8 Recently, several fentanyl analogs, such as carfentanyl 7 (Figure 1D), acetylfentanyl 1,9,10 (Figure 1A), acrylfentanyl 9,[11][12][13] (Figure 1C), and furanylfentanyl 7,8,[14][15][16][17] (Figure 1F) have been associated with acute intoxications worldwide. In Europe, between November 2015 and February 2017, 23 deaths were reported where furanylfentanyl was detected post-mortem.…”

Section: Introductionmentioning

confidence: 99%

Fast UHPLC–MS/MS method for analysis of furanylfentanyl in different seized blotter papers

Barbosa

Santos

Morais

et al. 2018

Drug Testing and Analysis

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Acrylfentanyl: Another new psychoactive drug with fatal consequences

Cited by 48 publications

References 15 publications

Correlations between metabolism and structural elements of the alicyclic fentanyl analogs cyclopropyl fentanyl, cyclobutyl fentanyl, cyclopentyl fentanyl, cyclohexyl fentanyl and 2,2,3,3-tetramethylcyclopropyl fentanyl studied by human hepatocytes and LC-QTOF-MS

Correlations between metabolism and structural elements of the alicyclic fentanyl analogs cyclopropyl fentanyl, cyclobutyl fentanyl, cyclopentyl fentanyl, cyclohexyl fentanyl and 2,2,3,3-tetramethylcyclopropyl fentanyl studied by human hepatocytes and LC-QTOF-MS

Detectability of fentanyl and designer fentanyls in urine by 3 commercial fentanyl immunoassays

Fast UHPLC–MS/MS method for analysis of furanylfentanyl in different seized blotter papers

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