Identification of novel psychoactive substances 25B-NBOMe and 4-CMC in biological material using HPLC-Q-TOF-MS and their quantification in blood using UPLC–MS/MS in case of severe intoxications

Wiergowski, Marek; Aszyk, Justyna; Kaliszan, Michał; Wilczewska, Kamila; Anand, Jacek Sein; Kot‐Wasik, Agata; Jankowski, Zbigniew

doi:10.1016/j.jchromb.2016.12.018

Cited by 33 publications

(18 citation statements)

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“…Once a particular constituent of "bath salts" is outlawed, new compounds with slightly modified chemical structures emerge, making synthetic cathinones the second largest group of NPSs monitored by the European Monitoring Centre for Drug and Drug Addiction (EMCDDA) (Coppola and Mondola 2012;EMCDDA 2019;Zawilska and Wojcieszak 2013). Chlorine-containing derivatives have become one of the most popular synthetic cathinones after the appearance of 4-chloromethcathinone (4-CMC; clephedrone) around 2014 (Taschwer et al 2014;Wiergowski et al 2017). Halogenated methcathinones, namely 4-CMC and 3chloromethcathinone (3-CMC), were among the five most frequently seized cathinones in Europe in 2016 (Białas et al 2017;EMCDDA 2018).…”

Section: Introductionmentioning

confidence: 99%

Four Synthetic Cathinones: 3-Chloromethcathinone, 4-Chloromethcathinone, 4-Fluoro-α-Pyrrolidinopentiophenone, and 4-Methoxy-α-Pyrrolidinopentiophenone Produce Changes in the Spontaneous Locomotor Activity and Motor Performance in Mice with Varied Profiles

2020

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Two chloromethcathinones, 3-chloromethcathinone (3-CMC) and 4-chloromethcathinone (4-CMC), and two para-substituted α-pyrrolidinophenones, 4-methoxy-α-pyrrolidinopentiophenone (4-MeO-PVP) and 4-fluoro-α-pyrrolidinopentiophenone (4-F-PVP), represent synthetic cathinones, the second most frequently abused group of new psychoactive substances (NPSs), which has aroused a worldwide health concern in the last decade. Synthetic cathinones act as psychostimulants by elevating extracellular levels of monoaminergic neurotransmitters. This study investigates effects of 3-CMC, 4-CMC, 4-MeO-PVP, and 4-F-PVP on the spontaneous locomotor activity and motor performance of mice. Additionally, neurotoxicity of substituted methcathinones against SH-SY5Y neuroblastoma cells was evaluated. All test cathinones stimulate in a dose-dependent manner horizontal locomotor activity of mice. Consistently to our prior findings, pyrrovalerones, but not methcathinone derivatives, produce dose-dependent elevation of vertical locomotor activity (rearing behavior). None of the tested compounds decreases the time spent on the accelerating rotarod, pointing to the lack of considerable motor disability in mice after acute exposition. Only 4-MeO-PVP at the high tested dose (20 mg/kg) increases motor performance of mice. Considering that α-pyrrolidinophenones are highly potent and selective DA uptake inhibitors, while chloromethcathinones enhance non-selective DA/5-HT release, we suggest that the increase of vertical locomotor activity and performance on rotarod in mice may serve as a behavioral indicator of the monoaminergic profile of synthetic cathinones. Finally, this study gives first insights into cytotoxicity of both 3-CMC and 4-CMC displayed against SH-SY5Y cells, which emerges and intensifies after prolonged incubation, suggesting the indirect mechanism of action, unrelated to interactions with monoamine transporters.

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Section: Introductionmentioning

confidence: 99%

Four Synthetic Cathinones: 3-Chloromethcathinone, 4-Chloromethcathinone, 4-Fluoro-α-Pyrrolidinopentiophenone, and 4-Methoxy-α-Pyrrolidinopentiophenone Produce Changes in the Spontaneous Locomotor Activity and Motor Performance in Mice with Varied Profiles

2020

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“…Due to the novelty of the drug, there is no data in scientific literature considering the pharmacokinetics, pharmacodynamics, pharmacological and toxicological effects, and the potential of acute overdose effects and addiction in a long period of time. Wiergowski et al [ 11 ] reported three cases of 4-CMC intake. However, these intoxication cases were considered also with a high dose administration of 25B-NBOMe.…”

Section: Introductionmentioning

confidence: 99%

Blood concentrations of a new psychoactive substance 4-chloromethcathinone (4-CMC) determined in 15 forensic cases

et al. 2018

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PurposeThe 4-chloromethcathinone (4-CMC) is a synthetic derivative of cathinone and belongs to new psychoactive substances. Neither data on the effects of 4-CMC on the human body, nor on nontoxic, toxic and lethal concentrations in biological materials have been published in the literature. This paper describes the results of an analysis of the blood concentrations of 4-CMC determined in 15 forensic cases related to nonfatal intoxication including driving under the influence, and fatalities including overdoses, suicide and traffic accidents.MethodsA new method for the quantification of 4-CMC using gas chromatography–mass spectrometry (GC–MS) was developed. The symptoms of 4-CMC use were also studied based on an analysis of the documents prepared during the collection of samples or at autopsies.ResultsThe limits of detection and quantification of the method for blood samples were 0.3 and 1 ng/mL, respectively. The calibration curve was linear in the studied concentration range (1–500 ng/mL) with the correlation coefficient at 0.9979. The extraction recoveries varied in the range of 94.3–98.8%. The accuracy and precision were acceptable. The determined concentrations in nonfatal cases ranged from 1.3 to 75.3 ng/mL, and in fatalities from 56.2 to 1870 ng/mL.ConclusionsOur study can assist in the recognition of the possible effects caused by 4-CMC and can be helpful during the preparation of forensic toxicological opinions for courts of law. The validation parameters indicate the sensitivity and accuracy of the method. This is the first work presenting a validated method for the determination of 4-CMC in blood samples by GC–MS.

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“…Blood: 25B-NBOMe, 661 ng/mL; 4-CMC, 0.8 ng/mL Wiergowski et al, 2017 The other two were aggressive and very agitated. They were shouting at each other, speaking illogically, screaming incomprehensibly and moving anxiously in the flat.…”

Section: Shintanimentioning

confidence: 98%

“…NBOMes produce an array of adverse effects (Hill et al, 2013;Rose et al, 2013;Bersani et al, 2014;EMCDDA, 2014;Forrester, 2014;Grautoff and Kähler, 2014;Lawn et al, 2014;Stellpflug et al, 2014;Suzuki et al, 2014;Tang et al, 2014;World Health Organization, 2014a,b;Hieger et al, 2015;Nikolaou et al, 2015;Poklis et al, 2015b;Srisuma et al, 2015;Wood et al, 2015;Gee et al, 2016;Kristofic et al, 2016;Hermanns-Clausen et al, 2017;Humston et al, 2017;Madsen et al, 2017;Rajotte et al, 2017;Schetz et al, 2017;Wiergowski et al, 2017;Zygowiec et al, 2017;Marchi et al, 2019;Erowid.org); for comprehensive reviews see Suzuki et al, 2015;Halberstadt, 2017).…”

Section: Effects Related To Use Of Nbomesunclassified

“…Patients with hematological disturbances require transfusion(s) of blood preparations (frozen plasma, frozen erythrocytes, or platelet concentrate). Severely aggressive patients may require antipsychotic drugs in addition to benzodiazepines (Hill et al, 2013;Rose et al, 2013;Forrester, 2014;Stellpflug et al, 2014;Hieger et al, 2015;Gee et al, 2016;Humston et al, 2017;Schetz et al, 2017;Wiergowski et al, 2017). Some emergency interventions are specifically intended to treat rhabdomyolysis, which may lead to severe complications, particularly acute kidney injury/failure and metabolic acidosis.…”

Section: Miscellaneousmentioning

confidence: 99%

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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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Identification of novel psychoactive substances 25B-NBOMe and 4-CMC in biological material using HPLC-Q-TOF-MS and their quantification in blood using UPLC–MS/MS in case of severe intoxications

Cited by 33 publications

References 50 publications

Four Synthetic Cathinones: 3-Chloromethcathinone, 4-Chloromethcathinone, 4-Fluoro-α-Pyrrolidinopentiophenone, and 4-Methoxy-α-Pyrrolidinopentiophenone Produce Changes in the Spontaneous Locomotor Activity and Motor Performance in Mice with Varied Profiles

Four Synthetic Cathinones: 3-Chloromethcathinone, 4-Chloromethcathinone, 4-Fluoro-α-Pyrrolidinopentiophenone, and 4-Methoxy-α-Pyrrolidinopentiophenone Produce Changes in the Spontaneous Locomotor Activity and Motor Performance in Mice with Varied Profiles

Blood concentrations of a new psychoactive substance 4-chloromethcathinone (4-CMC) determined in 15 forensic cases

NBOMes–Highly Potent and Toxic Alternatives of LSD

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