Nerve agents have been used recently in the Syrian civil war. Collecting relevant samples for retrospective identification of an attack is often problematic. The article deals with the possibility of using contaminated gloves as an analytical sample for evidence of the chemical weapons use. There have not yet been published studies dealing with the identification of chemical warfare agents in this type of matrix, where the diversity of chemical properties of gloves and the lifetime of the contaminated sample would be considered. Sarin, soman, and cyclosarin were used as contaminants in the study. Nitrile, latex, and vinyl disposable gloves were chosen as matrices. The identification method was gas chromatography. Six solvents commonly used in military laboratories were tested as extractants. The extraction procedure was optimized in terms of the appropriate method (vortex) and the required extraction time (1 min) and resulted in significant reduction in sample preparation time. The chromatographic background of the extracts was also monitored in order to find a method with the least number of peaks interfering in the identification. Suitable solvents were hexane and acetonitrile. The lifetime of the sample was also investigated. The worst result was recorded for latex. For individual contaminants, the time varied depending on the volatility. The developed procedures were successfully validated within a sample handling effects scenario. The results demonstrate that in the event of an ongoing military risk at the site of an attack, even discarded disposable rubber glove type samples can be used as evidence.
- MeSH
- guma * chemie MeSH
- latex MeSH
- nervová bojová látka * MeSH
- ochranné rukavice MeSH
- retrospektivní studie MeSH
- rozpouštědla MeSH
- Publikační typ
- časopisecké články 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.
- 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
Deschloroketamine (2-(methylamino)-2-phenyl-cyclohexanone) is a ketamine analog belonging to a group of dissociative anesthetics, which have been distributed within the illicit market since 2015. However, it was also being sold as 'ketamine' misleading people to believe that they were getting genuine ketamine. Dissociative anesthetics have also come to the attention of the psychiatric field due to their potential properties in the treatment of depression. At present, there is a dearth of information on deschloroketamine related to its metabolism, biodistribution, and its mechanism of action. We have therefore carried out a metabolomics study for deschloroketamine via non-targeted screening of urine samples employing liquid chromatography combined with high-resolution mass spectrometry. We developed and validated a multiple reaction monitoring method using a triple quadrupole instrument to track metabolites of deschloroketamine. Furthermore, significant metabolites of deschloroketamine, (trans-dihydrodeschloroketamine, cis- and trans-dihydronordeschloroketamine, and nordeschloroketamine), were synthesized in-house. The prepared standards were utilized in the developed multiple reaction monitoring method. The quantification method for serum samples provided intra-day accuracy ranging from 86% to 112% with precision of 3% on average. The concentrations of cis/trans-dihydronordeschloroketamines and trans-dihydrodeschloroketamine were lower than 10 ng/mL, nordeschloroketamine and deschloroketamine ranged from 0.5 to 860 ng/mL in real samples. The quantification method for brain tissue provided intra-day accuracy ranging from 80% to 125% with precision of 7% on average. The concentrations of cis/trans-dihydronordeschloroketamines and trans-dihydrodeschloroketamine ranged from 0.5 to 70 ng/g, nordeschloroketamine and deschloroketamine varied from 0.5 to 4700 ng/g in real samples.
- MeSH
- chromatografie kapalinová MeSH
- ketamin agonisté krev chemická syntéza farmakokinetika MeSH
- krysa rodu rattus MeSH
- mozek metabolismus MeSH
- tandemová hmotnostní spektrometrie přístrojové vybavení MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Agent BZ (3-quinuclidinyl benzilate) is a centrally acting synthetic anticholinergic agent, considered as a potential military incapacitating chemical warfare agent. Despite its significance as a model compound in pharmacological research and its potential misuse in chemical attacks, few modern analytical methods for BZ determination in biological samples have been published. The goal of the present work is to develop and validate a sensitive and rapid LC-MS/MS method for the determination of agent BZ in rat plasma. The sample preparation was based on solid-phase extraction on C-18 cartridges. The reversed-phase HPLC coupled with the mass spectrometer with electrospray ionization in the positive ion-selective reaction monitoring mode was employed in the BZ analysis. Atropine was used as an internal standard. The presented method is selective, accurate, precise, and linear (r2 = 0.9947) in a concentration range from 0.5 ng/mL to 1 000 ng/mL and sensitive enough (limit of detection 0.2 ng/mL; limit of quantification 0.5 ng/mL) to determine the BZ plasma levels in rats exposed to 2 mg/kg and 10 mg/kg of BZ. The highest level of BZ in plasma was observed 5 minutes after intramuscular administration (154.6 ± 22.3 ng/mL in rats exposed to 2 mg/kg of BZ and 1024 ± 269 ng/mL in rats exposed to 10 mg/kg). After 48 h, no BZ was observed at detectable levels. This new method allows the detection and quantification of BZ in biological samples after exposure of an observed organism and it will be further optimized for other tissues to observe the distribution of BZ in organs.
- MeSH
- chinuklidinylbenzilát analýza krev MeSH
- cholinergní antagonisté analýza krev MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- krysa rodu rattus MeSH
- limita detekce MeSH
- potkani Wistar MeSH
- tandemová hmotnostní spektrometrie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- validační studie MeSH
Over the past decade, the use of anabolic androgenic steroids (AAS) by recreational bodybuilders and regular gym members has been increasing exponentially. However, there is a lack of knowledge on AAS products sold in the Czech Republic and Slovakia. The aim of this study was to assess the quantity of active substances in AAS products obtained from AAS users in the Czech Republic and Slovakia. In addition, the study also examines the current trends in counterfeit AAS products used by recreational bodybuilders and regular gym members. For this purpose, the authors developed and validated a universal ultra-high performance liquid chromatography with tandem mass spectrometry method to determine the most popular doping substances in different pharmaceutical formulations (oil-based injectables, tablets, and capsules). This method was successfully utilized for the analysis of 358 AAS products. Our results showed that 58.9% AAS products analyzed contained the declared active substances at the declared concentrations, 15.9% contained no active substance, 16.8% were under-concentrated, 4.5% contained active substances different from those declared on the label, and 3.6% products were over-concentrated. Alarmingly, the results demonstrated that over 40% of the AAS analyzed failed to meet label claims and therefore may pose serious health risks to consumers. This study also highlighted that the availability of AAS should be more rigorously restricted and their quality closely monitored in order to protect AAS users. In conclusion, the authors have developed a precise, accurate, sensitive, selective, and robust method for the routine screening of products containing anabolic androgenic steroids.
- MeSH
- injekce statistika a číselné údaje MeSH
- kongenery testosteronu analýza ekonomika MeSH
- lidé MeSH
- tablety MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- tobolky MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- zločin ekonomika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
Procedures for the extraction-spectrophotometric determination of tris(2-chloroethyl)amine, an alkylating agent known as a drug as well as a chemical warfare agent (nitrogen mustard HN-3), with 7 acid-base indicators of a triphenylmethane lactone type, phthaleins, were developed. Representatives of phthaleins without an oxygen bridge (thymolphthalein, o-cresolphthalein, naphtholphthalein) and with an oxygen bridge (fluorescein, 2',7'-dichlorofluorescein, eosin B and eosin Y) were used. The methods were based on the formation of ion pair complexes. Chloroform was used as a non-polar solvent for an extraction. The conditions to determine were optimized for the optimal pH of the buffer and the concentration of a phthalein as a reagent. The dependence on the reaction time in a water phase and the stoichiometry of extraction products were studied. The detection limits and the limits of the determination of separate procedures and conditional extraction constants were determined. Comparison with the spectrophotometric method of the group determination of alkyl halides and acyl halides using alkaline ethanol-water solution of thymolphthalein, the so-called T-135 agent, was conducted. While studying the selectivity, the possible interference of bis(2-chloroethyl)sulphide and 3 nitrogen mustards in the proposed procedures were verified. Copyright © 2016 John Wiley & Sons, Ltd.
- MeSH
- alkylační látky analýza izolace a purifikace MeSH
- chemické bojové látky analýza izolace a purifikace MeSH
- fenolftaleiny chemie MeSH
- koncentrace vodíkových iontů MeSH
- limita detekce MeSH
- pufry MeSH
- sloučeniny dusíkatého yperitu analýza izolace a purifikace MeSH
- spektrofotometrie metody MeSH
- voda analýza MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
Avidin-biotin technology was used for the implementation of an enzyme-linked immunosorbent assay (AB-ELISA) as a sensitive method for the detection of anabolic androgenic steroids (AAS) present in dietary supplements. Using click chemistry, novel haptens (linker-optimized biotinylated nandrolone (NT) and testosterone (T) at positions C-3 and C-17, respectively) were designed and synthesized to be then applied as four different immobilized competitors in a proposed set of four indirect competitive AB-ELISAs. Four rabbit polyclonal antibodies of various specificities were prepared using four different immunogens synthesized from C-3 and C-17 carboxymethyloxime and hemisuccinate derivatives of NT and T, respectively. Assembled AB-ELISAs were characterized to establish method parameters such as a half-maximum inhibition concentration (0.18-12.99 ng/mL), limit of detection (0.004-0.032 ng/mL) and linear working range (the best with 0.02-1.38 ng/mL). The stability of the set simulating storage in different conditions was demonstrated. Cross reactivity (CR) was tested for 59 steroids including both endogenous and synthetic analogues in four assembled AB-systems. The focus was placed on the practical use of the method in detection of various AAS in 49 samples of counterfeit dietary supplements. The concordance between ultra high performance liquid chromatography-mass spectrometry (UHPLC-MS) and the CR corrected data from AB-ELISA indicated the potential of this method even to quantification of T propionate, NT phenyl propionate, and NT decanoate in such a complex matter. Copyright © 2016 John Wiley & Sons, Ltd.
- MeSH
- anabolika analýza MeSH
- avidin chemie MeSH
- biotin chemie MeSH
- ELISA metody MeSH
- králíci MeSH
- limita detekce MeSH
- nandrolon analýza MeSH
- potravní doplňky analýza MeSH
- testosteron analýza MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
The present in vitro study was designed to test and compare anthelmintic activity, hepatotoxicity, and biotransformation of four selected aminoacetonitrile derivatives (AADs): monepantel (MOP, anthelmintic approved for the treatment), AAD-970, AAD-1154, and AAD-1336. Micro-agar larval development test, MTT test of cytotoxicity, and biotransformation study coupled with Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique were used for this purpose. Larvae of two Haemonchus contortus strains (drug susceptible and multi-drug resistant) and primary cultures of rat and ovine hepatocytes served as model systems. All AADs (including MOP) exhibited significant larvicidal effect in H. contortus susceptible as well as multi-resistant strains, much higher than those of reference anthelmintics thiabendazole and flubendazole. AAD-1154 provides the best results for most tested parameters among all AADs in this study. The cytotoxicity test showed that all AADs can be considered as nontoxic for hepatocytes. In the biotransformation study, Phase I and Phase II metabolites of AADs were identified and schemes of possible metabolic pathways in ovine hepatocytes were proposed. Biotransformation of MOP was much more extensive than biotransformation of other AADs. Based on obtained results, AAD-1154 and AAD-1336 can be considered as promising candidates for further in vivo testing.
- MeSH
- aminoacetonitrily analogy a deriváty analýza farmakokinetika toxicita MeSH
- anthelmintika analýza farmakokinetika toxicita MeSH
- biotransformace MeSH
- Haemonchus účinky léků MeSH
- hepatocyty metabolismus MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- larva MeSH
- mebendazol analogy a deriváty analýza farmakokinetika MeSH
- ovce MeSH
- potkani Wistar MeSH
- tandemová hmotnostní spektrometrie MeSH
- thiabendazol analýza farmakokinetika MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Monepantel (MOP) is a new anthelmintic drug intended for the treatment and control of gastrointestinal roundworms (nematodes) infection and associated disease in sheep. The aim of our study was to find out metabolic pathways of MOP in sheep in vivo and in its parasite Haemonchus contortus ex vivo. MOP biotransformation in two H. contortus strains with different sensitivity to anthelmintics was also compared. Ultra high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) technique is used for the identification of MOP metabolites in ovine urine, faeces, and nematodes. MOP biotransformation study in sheep in vivo led to the identification of 13 MOP metabolites; 7 of them have not been described previously in in vitro study. The study of MOP biotransformation in H. contorus ex vivo reveals four MOP metabolites. The nitrile hydrolysis as a new biotransformation pathway in helminths ex vivo is reported here for the first time. Unlike sheep, H. contorus nematodes are not able to metabolize MOP via phase II biotransformation. Nematodes of resistant White river (WR) strain form more types of MOP metabolites than nematodes of sensitive inbred susceptible Edinburgh (ISE) strain. Based on obtained results, schemes of metabolic pathways of MOP in sheep and nematodes are proposed.
- MeSH
- aminoacetonitrily analogy a deriváty analýza metabolismus MeSH
- anthelmintika analýza metabolismus MeSH
- Haemonchus účinky léků metabolismus MeSH
- ovce MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
