BACKGROUND: Sub/supercritical fluid chromatography is regarded as a greener separation technique due to the use of carbon dioxide as the main component of the mobile phase compared to conventional liquid chromatography techniques. Organic co-solvents are usually added to carbon dioxide to increase elution strength of the mobile phase. Therefore, it is of great importance to test applicability of green co-solvents in separation methods and to include them among commonly used mobile phase components. RESULTS: A comprehensive study of the suitability of green solvent dimethyl carbonate as a co-solvent for enantioseparation in sub/supercritical fluid chromatography was conducted with a set of novel psychoactive substances from various groups. The experiments were performed on polysaccharide-based columns. For successful enantioseparation of these compounds, the presence of basic or mixed mobile phase additives was essential. The obtained results clearly show that dimethyl carbonate is a suitable co-solvent for enantioseparation on polysaccharide-based columns in sub/supercritical fluid chromatography and in some cases surpasses commonly used co-solvents as methanol and propan-2-ol. SIGNIFICANCE: The use of more sustainable co-solvents, such as dimethyl carbonate, instead of conventional ones to carbon dioxide presents a greener approach to analytical applications and reduces the overall environmental impact of analytical processes.

• Klíčová slova
• Dimethyl carbonate, Enantioseparation, Novel psychoactive substances, Polysaccharide-based column, Sub/supercritical fluid chromatography,
• MeSH
• formiáty chemie   MeSH
• psychotropní léky * izolace a purifikace   chemie   MeSH
• rozpouštědla chemie   MeSH
• stereoizomerie MeSH
• superkritická fluidní chromatografie * metody   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• formiáty MeSH
• methyl carbonate MeSH Prohlížeč
• psychotropní léky * MeSH
• rozpouštědla MeSH

The dark web scene has been drawing the attention of law enforcement agencies and researchers alike. To date, most of the published works on the dark web are based on data gained by passive observation. To gain a more contextualized perspective, a study was conducted in which three vendors were selected on the "Dream Market" dark web marketplace, from whom subsequently several new psychoactive substances (NPS) were ordered. All transactions were documented from the initial drug deal solicitation to the final qualitative analysis of all received samples. From the selected vendors, a total of nine NPS samples was obtained, all of which were analyzed by NMR, HRMS, LC-UV, and two also by x-ray diffraction. According to our analyses, four of the five substances offered under already known NPS names contained a different NPS. The selected vendors therefore either did not know about their product, or deliberately deceived the buyers. Furthermore, two of three obtained samples of purportedly novel NPS were identified as already documented substances sold under a different name. However, the third characterized substance sold as "MPF-47700" was a novel, yet uncharacterized, NPS. Finally, we received a single undeclared substance, later identified as 5F-ADB. In addition to chemical analysis of the nine obtained NPS samples, the methodology used also yielded contextual information about the accessibility of NPS on the dark web, the associated purchase process, and the modus operandi of three NPS vendors. Direct participation in dark web marketplaces seems to provide additional layers of information useful for forensic studies.

• Klíčová slova
• Dream Market, MPF-47700, dark web, darknet, new psychoactive substances,
• MeSH
• hmotnostní spektrometrie MeSH
• internet MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• obchodování s drogami * MeSH
• odhalování abúzu drog MeSH
• psychotropní léky analýza   zásobování a distribuce   MeSH
• spektrofotometrie ultrafialová MeSH
• zakázané drogy analýza   zásobování a distribuce   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• psychotropní léky MeSH
• zakázané drogy MeSH

INTRODUCTION AND AIMS: New psychoactive substances (NPS) represent hundreds of novel compounds. However, the general public might not be familiar with the overarching term NPS. This can result in both under- and over-reporting of NPS use. DESIGN AND METHODS: The study analysed the last-year prevalence of NPS use in an online survey conducted across I-TREND project countries (the Czech Republic, the Netherlands and Poland). Self-reported NPS use was assessed within two types of questions-a generic and a checklist question. We analysed prevalence for each question separately, incorporated the free-text probe 'other' that followed them, and combined the two questions into a conservative and an inclusive estimate. RESULTS: Including free-text responses to the 'other' categories increased prevalence of NPS use (from 51% to 56% for the checklist question and 25% to 32% for the generic question). Taking an inclusive approach to estimating prevalence (i.e. indicating NPS use in either a generic list or from the checklist) yielded a higher prevalence estimate (60%, 95% confidence interval 58-62%), compared to a more conservative approach in which NPS use had to be affirmed by both questions (27%, 95% confidence interval 26-29%). DISCUSSION AND CONCLUSIONS: Generic questions might lead to notably lower estimates of self-reported NPS use in comparison to checklists. However, creating relevant checklists is challenging and lengthy survey instruments have limitations. Further surveys might benefit from featuring a combination of the strategies used in this study-a single (generic) question involving a number of locally specific NPSs and a free-text 'other' probe.

• Klíčová slova
• NPS checklist, new psychoactive substances, online survey, self-reported prevalence, validity,
• MeSH
• dospělí MeSH
• lidé MeSH
• poruchy spojené s užíváním psychoaktivních látek epidemiologie   MeSH
• prevalence MeSH
• průzkumy a dotazníky * MeSH
• psychotropní léky aplikace a dávkování   MeSH
• sběr dat metody   MeSH
• zakázané drogy MeSH
• zpráva o sobě MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Nizozemsko epidemiologie   MeSH
• Polsko epidemiologie   MeSH
• Názvy látek
• psychotropní léky MeSH
• zakázané drogy MeSH

Novel psychoactive substances (NPS) are synthetic compounds that have been designed to produce the physiological and psychological effects of known recreational drugs, while circumventing current drug control laws and scheduling guidelines. Such "designer drugs" pose problems in detection and prevention of use, and they are no less dangerous than known controlled substances. Among the various classes of NPS, many are chiral. As they are synthetic products, most are racemates. Not unexpectedly, there is limited information about different the pharmacological and toxicological properties of their pure enantiomers. Hence, fast and reliable enantioselective methods are of great interest. In this work, superficially porous particle (SPP) vancomycin-based chiral stationary phases were used for development of fast enantioselective separation methods for various classes of NPS in supercritical fluid chromatography and liquid chromatography. The NPS tested included pyrovalerones, benzofurans, phenidines and phenidates. The effect of mobile phase composition on the retention and resolution of NPS in supercritical fluid chromatography was examined. The amount as well as the ratios of additives used is crucial for enantioseparation efficiency. Results showed the high enantioselective potential of vancomycin-based columns in both chromatographic techniques; 88% of NPS tested were enantioseparated in supercritical fluid chromatography and 69% of NPS tested were enantioseparated in liquid chromatography. Moreover, under optimized conditions, simultaneous enantioseparations of some NPS were achieved, which indicates great suitability of vancomycin-based columns for this purpose. The proposed methods can serve as guides for method development and for enantioseparation of further upcoming NPS.

• Klíčová slova
• Enantioseparation, HPLC, Novel psychoactive substances, SFC, Vancomycin,
• MeSH
• benzofurany chemie   MeSH
• poréznost MeSH
• psychotropní léky chemie   MeSH
• rozpouštědla chemie   MeSH
• stereoizomerie MeSH
• superkritická fluidní chromatografie metody   MeSH
• vankomycin chemie   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzofurany MeSH
• psychotropní léky MeSH
• rozpouštědla MeSH
• vankomycin MeSH

The black market for new psychoactive substances has been constantly evolving and the substances that appear on this market cause a considerable number of issues, in extreme cases leading to human deaths. While monitoring the drug black market, we detected a sample of a dissociative anesthetic methoxphenidine, the salt of which contained an unusual anion in the form of bromo- and chloro-zincate complex. Concerning the unknown and potentially hazardous properties of this sample, we performed an in vitro cytotoxicity screening in cell lines of various origins (e.g., kidney, liver, bladder) which was compared with the toxicity results of the methoxphenidine standard prepared for this purpose. The street methoxphenidine sample exhibited markedly higher toxicity than the standard, which was probably caused by the anion impurity. Since it is not usual to analyze anions in salts of novel psychoactive substances, but such samples may be commonly available at the drug black market, we have developed a method for their identification with X-ray powder diffraction (XRPD), which also enabled us to distinguish between different polymorphs/solvates of methoxphenidine that were crystallized in the laboratory. XRPD offers additional data about samples, which may not be discovered by routine techniques, and in some cases, they may help to find out essential information.

• Klíčová slova
• X-ray powder diffraction, crystal structure, cytotoxicity, dissociative anesthetic, inorganic impurity, methoxphenidine, new psychoactive substances, novel synthetic drug,
• MeSH
• anestetika disociativní škodlivé účinky   MeSH
• difrakce rentgenového záření metody   MeSH
• kultivované buňky MeSH
• lidé MeSH
• piperidiny škodlivé účinky   MeSH
• psychotropní léky škodlivé účinky   MeSH
• zakázané drogy škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 1-(1-(2-methoxyphenyl)-2-phenylethyl)piperidine MeSH Prohlížeč
• anestetika disociativní MeSH
• piperidiny MeSH
• psychotropní léky MeSH
• zakázané drogy MeSH

Naphyrone, also known as NRG-1, is a novel psychoactive substance (NPS), a cathinone with stimulatory properties available on the grey/illicit drug market for almost a decade. It is structurally related to infamously known powerful stimulants with the pyrovalerone structure, such as alpha-pyrrolidinovalerophenone (α-PVP) or methylenedioxypyrovalerone (MDPV) that are labeled as a cheap replacement for cocaine and other stimulants. Despite the known addictive potential of α-PVP and MDPV, there are no studies directly evaluating naphyrone's addictive potential e.g., in conditioned place preference (CPP) test or using self-administration. Therefore, our study was designed to evaluate the addictive potential in a CPP test in male Wistar rats and compare its effect to another powerful stimulant with a high addictive potential - methamphetamine. Naphyrone increased time spent in the drug-paired compartment with 5 and 20 mg/kg s.c. being significant and 10 mg/kg s.c. reaching the threshold (p = 0.07); the effect was comparable to that of methamphetamine 1.5 mg/kg s.c. The lowest dose, naphyrone 1 mg/kg s.c., had no effect on CPP. Interestingly, no dose response effect was detected. Based on these data, we are able to conclude that naphyrone has an addictive potential and may possess a significant risk to users.

• Klíčová slova
• Addictive potential, CPP, Conditioned place preference test, Naphyrone, Novel psychoactive substances,
• MeSH
• alkaloidy farmakologie   MeSH
• chování zvířat účinky léků   MeSH
• klasické podmiňování účinky léků   MeSH
• krysa rodu Rattus MeSH
• methamfetamin aplikace a dávkování   farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• pentanony aplikace a dávkování   farmakologie   MeSH
• poruchy spojené s užíváním psychoaktivních látek * MeSH
• potkani Wistar MeSH
• pyrrolidiny aplikace a dávkování   farmakologie   MeSH
• stimulanty centrálního nervového systému aplikace a dávkování   farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-naphthalen-2-yl-2-pyrrolidin-1-ylpentan-1-one MeSH Prohlížeč
• alkaloidy MeSH
• cathinone MeSH Prohlížeč
• methamfetamin MeSH
• pentanony MeSH
• pyrrolidiny MeSH
• stimulanty centrálního nervového systému MeSH

Recreational use of the potent synthetic opioid 3,4- dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide (U-47700) is rising, accompanied by increasingly frequent cases of serious intoxication. This article reports a case of near-fatal U-47700 intoxication. A man was found unconscious (with drug powder residues). After 40 h in hospital (including 12 h of supported ventilation), he recovered and was discharged. Liquid chromatography/high-resolution mass spectrometry (LC/HRMS) or gas chromatography/mass spectrometry (GC/MS) were used to detect and quantify substances in powders, serum and urine. Powders contained U-47700 and two synthetic cannabinoids. Serum and urine were positive for U-47700 (351.0 ng/mL), citalopram (

• Klíčová slova
• 3,4- dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide, U47700, clonazolam, forensic science, forensic toxicology, novel benzodiazepine, novel psychoactive substance, synthetic opioid,
• MeSH
• benzamidy škodlivé účinky   analýza   MeSH
• benzodiazepiny analýza   MeSH
• chromatografie kapalinová MeSH
• citalopram analýza   MeSH
• dospělí MeSH
• hmotnostní spektrometrie MeSH
• lidé MeSH
• midazolam analýza   MeSH
• odhalování abúzu drog MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• předávkování léky * MeSH
• soudní toxikologie MeSH
• zakázané drogy škodlivé účinky   analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• benzamidy MeSH
• benzodiazepiny MeSH
• citalopram MeSH
• midazolam MeSH
• U-47700 MeSH Prohlížeč
• zakázané drogy MeSH

Among different substance classes, New Psychoactive Substances (NPS) comprise chiral amphetamines for stimulant and empathic effects. There is little knowledge in terms of clinical studies about possibly different effects of the two enantiomers of novel amphetamine derivatives. For this reason, there is a big demand for enantioseparation method development of this new substance class. Regarding gas chromatography, cyclodextrins proved to be effective for enantioseparation of NPS. In our attempt, an Astec® Chiraldex™ G-PN column containing 2,6-di-O-pentyl-3-propionyl-γ-cyclodextrin and a Lipodex™ D column containing heptakis-(2,6-di-O-pentyl-O-acetyl)-β-cyclodextrin as chiral selector served as stationary phases in a Shimadzu GCMS-QP2010 SE system. Because of the special coating, maximum temperature is limited to 200 °C isothermal or 220 °C in programmed mode. To ensure detection, trifluoroacetic anhydride (TFAA) was used to increase sample volatility.1 As a result, 35 amphetamines were tested as their TFAA-derivatives. A screening method with a temperature gradient from 140 °C to 200 °C at a heating ramp of 1 °C per minute and final time of 5 min, showed baseline separation for seven and partial separations for 16 trifluoro acetylated amphetamines using the Chiraldex™ G-PN column. Six baseline and nine partial separations were observed with the Lipodex™ D column, respectively.

• Klíčová slova
• GC, MS, NPS, benzofurans, benzofurys, chiral, cyclodextrin, designer drugs, novel psychoactive substances,
• MeSH
• amfetaminy * chemie   izolace a purifikace   MeSH
• chromatografie plynová metody   MeSH
• cyklodextriny chemie   MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí metody   MeSH
• stereoizomerie MeSH
• teplota MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amfetaminy * MeSH
• cyklodextriny MeSH

Kratom is a mixture of compounds that are present in the leaves of the tropical tree Mitragyna speciosa. It is used as a psychoactive agent with both opiate and stimulant-like effects. In this case series we describe the signs, symptoms, and the management of kratom overdose in the prehospital setting and in intensive care. We retrospectively searched for cases in the Czech Republic. Over 36 months we found 10 cases of kratom poisoning, which healthcare records were analyzed and reported as per CARE guidelines. The dominant symptoms in our series were neurological and included quantitative (n = 9) or qualitative (n = 4) disorder of consciousness. Signs and symptoms of vegetative instability [hypertension (n = 3) and tachycardia (n = 3) vs. bradycardia/cardiac arrest (n = 2), mydriasis (n = 2) vs. miosis (n = 3)] were noticed. Prompt response to naloxone in two cases and lack of response in one patient were observed. All patients survived and the effect of intoxication wore off within two days. Kratom overdose toxidrome is variable and, in keeping with its receptor physiology, consists of signs and symptoms of opioid-like overdose, sympathetic overactivation and serotonin-like syndrome. Naloxone can help to avoid intubation in some cases.

• Klíčová slova
• Case series, Mitragyna speciosa, Novel psychoactive substance (NPS), Opioid-like intoxication, Plant toxin,
• MeSH
• lidé MeSH
• listy rostlin MeSH
• Mitragyna * MeSH
• naloxon MeSH
• opioidní analgetika MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• naloxon MeSH
• opioidní analgetika MeSH

N-(2-methoxybenzyl)phenethylamines (NBOMes) are a family of potent 5-HT2A agonists containing substances emerging on the illicit drug market as a replacement for N,N-diethyllysergamide (LSD). Despite the increasing use of NBOMes for diagnostic, research and recreational purposes, only a limited number of studies have focussed on their in vivo effect. Here, we investigated pharmacokinetics, systemic toxicity, thermoregulation in individually and group-housed animals, and acute behavioural effects after subcutaneous administration of 2,5-dimethoxy-4-(2-((2-methoxybenzyl)amino)ethyl)benzonitrile (25CN-NBOMe; 0.2, 1, and 5 mg/kg) in Wistar rats. Drug concentration peaked 1 h after the administration of 5 mg/kg in both blood serum and brain tissue with a half-life of 1.88 and 2.28 h, respectively. According to Organisation for Economic Co-operation and Development 423 toxicity assay, the drug is classified into category 3 with a lethal dose of 300 mg/kg and an estimated LD50 value of 200 mg/kg. Histological examination of organs collected from rats injected with the lethal dose revealed subtle pathological changes, highly suggestive of acute cardiovascular arrest due to malignant arrhythmia. Altered thermoregulation after 5 mg/kg was demonstrated by reduced body temperature in individually housed rats (p < 0.01). Behavioural effects assessed by the Open Field test and Prepulse Inhibition of Startle Response revealed that the two lower doses (0.2 and 1 mg/kg) caused a reduction in locomotor activity (p < 0.01), increased anxiety (p < 0.05) and 5 mg/kg additionally impaired sensorimotor gating (p < 0.001). In summary, 25CN-NBOMe readily passes the blood-brain barrier and exhibits a moderate level of toxicity and behavioural effect comparable with other NBOMes.

• Klíčová slova
• 25CN-, NBOMe, Wistar rat, behavioural study, novel psychoactive substances, toxicity,
• MeSH
• fenethylaminy MeSH
• halucinogeny * farmakologie   MeSH
• krysa rodu Rattus MeSH
• potkani Wistar MeSH
• termoregulace MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fenethylaminy MeSH
• halucinogeny * MeSH