Retrospective identification of 25I-NBOMe metabolites in an intoxication case

Richeval, Camille; Boucher, Alexandra; Humbert, Luc; Phanithavong, Mélodie; Wiart, Jean-François; Moulsma, Mustapha; Citterio-Quentin, Antony; Coulon, Thierry; Hernu, Romain; Vial, Thierry; Allorge, Delphine; Gaulier, Jean‐Michel

doi:10.1016/j.toxac.2017.01.001

Cited by 7 publications

(8 citation statements)

References 28 publications

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“…HLM incubates were prepared as already reported [23][24][25][26]. Once thawed, HLMs (2 mg protein/mL for a final volume of 100 µL) were pre- Fifty µL of a cofactor mixture (5 mM UDPGA, 1.3 mM NADPH, 3.3 mM G6P and 0.5 U/mL G6PD) in 0.1 M Tris-HCl was then added.…”

Section: Hlm Incubatesmentioning

confidence: 99%

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In vitro Characterization of NPS Metabolites Produced by Human Liver Microsomes and the HepaRG Cell Line Using Liquid Chromatographyhigh Resolution Mass Spectrometry (LC-HRMS) Analysis: Application to Furanyl Fentanyl

Richeval

Gicquel

Hugbart

et al. 2018

CPB

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Section: Hlm Incubatesmentioning

confidence: 99%

“…Screening for Fu-F metabolites was performed using a previously reported LC-HRMS method [23][24][25][26]…”

Section: Lc-hrms Analysismentioning

confidence: 99%

In vitro Characterization of NPS Metabolites Produced by Human Liver Microsomes and the HepaRG Cell Line Using Liquid Chromatographyhigh Resolution Mass Spectrometry (LC-HRMS) Analysis: Application to Furanyl Fentanyl

Richeval

Gicquel

Hugbart

et al. 2018

CPB

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“…OcF incubation with HLMs was performed using a previously reported method . Once thawed, HLMs (2 mg protein/mL for a final volume of 100 μL) were pre‐activated by alamethicin on ice (at 0.1 mmo/L) in an intermediate volume of 50 μL in 0.1 M Tris‐HCl‐MgCl 2 (10 mM MgCl 2 and 100 mM Tris‐HCl solution) at pH 7.4.…”

Section: Methodsmentioning

confidence: 99%

“…Screening for OcF metabolites was performed using a previously reported LC-HRMS method. 20,[25][26][27]32 LC-HRMS settings…”

Section: Lc-hrms Analysismentioning

confidence: 99%

Fatality involving ocfentanil documented by identification of metabolites

Allibe

Richeval

Phanithavong

et al. 2017

Drug Testing and Analysis

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The use of new psychoactive substances (NPS) has rapidly increased over the last decade. In the last 4 years, producers increasingly appear to be targeting non-controlled synthetic opioids, involving fentanyl derivatives such as ocfentanil (OcF). Identification of metabolites is of major importance in the context of NPS use, as it could improve the detection window in biological matrices in clinical and forensic intoxication cases. Hence, this work aims to report a fatality involving OcF documented by the identification of metabolites. A 30-year-old woman was found dead at home: an unidentified powder was found near her body and some injection sites were found at the autopsy. Toxicological analyses allowed to determine the presence of OcF in the powder, blood (3.7/3.9 μg/L, peripheral/cardiac) and in other post-mortem samples. The most relevant potential CYP- and UGT-dependent metabolites of OcF were investigated in vitro using human liver microsome incubation and liquid chromatography coupled with high resolution mass spectrometry, and subsequently confirmed in post-mortem samples. Four OcF metabolites were produced in vitro (a mono-hydroxylated OcF, O-desmethylOcF, a hydroxylated desmethylOcF and a glucuronidated form of the O-desmethylOcF), and all except the glucuronide were observed in blood and bile post-mortem samples. Considering the relative intensity of the chromatographic peak areas, O-desmethylOcF can be suggested to be an abundant metabolite of OcF. Nevertheless, the relevance of O-desmethylOcF as being a complementary analytical target of OcF for OcF use detection needs further in vivo confirmation, especially through analysis of urines from users.

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“…One sample contained 25I-NBOMe together with 15 metabolites, while the other contained no parent 25I-NBOMe; it was found to contain three O-demethyl metabolites. Seven 25I-NBOMe metabolites were detected in the urine of a severely intoxicated man: two demethyl-25I-NBOMe, one demethyl-hydroxy-25I-NBOMe, one hydroxy-25I-NBOMe, one di-demethyl-25I-NBOMe, one demethyl-25I-NBOMe glucuronide, and one hydroxy-25I-NBOMe glucuronide (Richeval et al, 2017). The presence of 25H-NBOMe in biological samples of people who used both 25B-NBOMe and 25I-NBOMe (Soh and Elliott, 2014;Stellpflug et al, 2014) suggests an alternative route of NBOMes biotransformation, i.e., removal of the halogen atom.…”

Section: Biotransformationmentioning

confidence: 99%

NBOMes–Highly Potent and Toxic Alternatives of LSD

2020

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Recently, a new class of psychedelic compounds named NBOMe (or 25X-NBOMe) has appeared on the illegal drug market. NBOMes are analogs of the 2C family of phenethylamine drugs, originally synthesized by Alexander Shulgin, that contain a N-(2-methoxy)benzyl substituent. The most frequently reported drugs from this group are 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe. NBOMe compounds are ultrapotent and highly efficacious agonists of serotonin 5-HT 2A and 5-HT 2C receptors (Ki values in low nanomolar range) with more than 1000-fold selectivity for 5-HT 2A compared with 5-HT 1A. They display higher affinity for 5-HT 2A receptors than their 2C counterparts and have markedly lower affinity, potency, and efficacy at the 5-HT 2B receptor compared to 5-HT 2A or 5-HT 2C. The drugs are sold as blotter papers, or in powder, liquid, or tablet form, and they are administered sublingually/buccally, intravenously, via nasal insufflations, or by smoking. Since their introduction in the early 2010s, numerous reports have been published on clinical intoxications and fatalities resulting from the consumption of NBOMe compounds. Commonly observed adverse effects include visual and auditory hallucinations, confusion, anxiety, panic and fear, agitation, uncontrollable violent behavior, seizures, excited delirium, and sympathomimetic signs such mydriasis, tachycardia, hypertension, hyperthermia, and diaphoresis. Rhabdomyolysis, disseminated intravascular coagulation, hypoglycemia, metabolic acidosis, and multiorgan failure were also reported. This survey provides an updated overview of the pharmacological properties, pattern of use, metabolism, and desired effects associated with NBOMe use. Special emphasis is given to cases of nonfatal and lethal intoxication involving these compounds. As the analysis of NBOMes in biological materials can be challenging even for laboratories applying modern sensitive techniques, this paper also presents the analytical methods most commonly used for detection and identification of NBOMes and their metabolites.

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Retrospective identification of 25I-NBOMe metabolites in an intoxication case

Cited by 7 publications

References 28 publications

In vitro Characterization of NPS Metabolites Produced by Human Liver Microsomes and the HepaRG Cell Line Using Liquid Chromatographyhigh Resolution Mass Spectrometry (LC-HRMS) Analysis: Application to Furanyl Fentanyl

In vitro Characterization of NPS Metabolites Produced by Human Liver Microsomes and the HepaRG Cell Line Using Liquid Chromatographyhigh Resolution Mass Spectrometry (LC-HRMS) Analysis: Application to Furanyl Fentanyl

Fatality involving ocfentanil documented by identification of metabolites

NBOMes–Highly Potent and Toxic Alternatives of LSD

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