RESUMO
The number of methods for the analysis of new psychoactive substances (NPS) is continually increasing, and there is no indication that this trend will change in the near future. The constantly growing market of "designer drugs" makes it necessary to develop new methods of their analysis. The aim of this review is to present the multi-component methods of detection and identification of NPS using low-resolution tandem mass spectrometry coupled with liquid chromatography. For this purpose, 36 articles were selected by applying strictly defined search criteria. Due to the large differences in the matrices and physicochemical properties of the analytes, the described research methods are diverse. These differences are visible in sample preparation methods, chromatographic columns, mobile phases, gradients, or additives to mobile phases used. This work collects and organizes the existing information on the subject of NPS screening analysis methods and will be helpful to forensic scientists working on this topic.
Assuntos
Detecção do Abuso de Substâncias , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Detecção do Abuso de Substâncias/métodos , Psicotrópicos/análise , Cromatografia Líquida/métodosRESUMO
PURPOSE: Over the last decade, there has been a significant growth in the market and number of new psychoactive substances (NPS). One of the NPS groups that has grown rapidly in recent years, bringing a new set of problems, consists of new synthetic opioids. The extreme potency of these compounds poses a high risk of acute poisoning, as an overdose can cause respiratory depression. Most of the information regarding human pharmacokinetics of new opioids is based on toxicological case reports and the data on concentrations of new opioids in human blood are scarce. The interpretation of results usually requires a comparison to previously published cases; therefore, a referenced compilation of previously published concentration data would be useful. METHODS: The data were collected by searching the PubMed and Scopus databases and by using the Google search engine. All the available data from articles and reports that measured new opioid concentrations in plasma, serum, or whole blood were included in the data analysis. RESULTS: The presented tables list the observed concentrations in fatal and nonfatal cases involving 37 novel synthetic opioids. CONCLUSIONS: Blood levels of new opioids are extremely difficult to interpret. Low blood concentrations of these substances do not rule out acute poisoning as their high potency creates a risk of respiratory depression even at low doses. Opioid tolerance, frequent presence of other drugs, and additional diseases make it impossible to define concentration ranges, especially the minimum fatal concentrations. This report provides quick access to the source articles quantifying novel synthetic opioids.
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Overdose de Drogas , Insuficiência Respiratória , Analgésicos Opioides/análise , Tolerância a Medicamentos , Fentanila , HumanosRESUMO
Synthetic cannabinoids (SCs) remain one of the largest groups of new psychoactive substances. Recently, new synthetic cannabinoids 5F-MDMB-PICA and 4F-MDMB-BINACA are increasing in popularity. A 33-year-old man lost consciousness after smoking an unknown substance. A glass pipe and two lumps of substance that turned out to contain 5F-MDMB-PICA and 4F-MDMB-BINACA were found at the scene. Blood, urine and cerebrospinal fluid were collected during the examination of the body. The synthetic cannabinoids were isolated from autopsy materials by precipitation with acetonitrile and extraction with ethyl acetate. The screening and quantitative analyses were performed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The liquid chromatography-quadrupole/time of flight mass spectrometry (LC-Q/TOF) technique was used for metabolite identification. 5F-MDMB-PICA was detected and quantified in all analysed materials, whereas 4F-MDMB-BINACA was found only in cerebrospinal fluid. The determined concentrations of 5F-MDMB-PICA were 0.9 (blood), 0.1 (urine) and 3.2 ng/mL (cerebrospinal fluid). The concentration of 4F-MDMB-BINACA in cerebrospinal fluid was 0.1 ng/mL. The main metabolites of both compounds (hydrolysis and oxidative defluorination) were found in all analysed body fluids. Cerebrospinal fluid may be important alternative material in autopsy cases. Rapid elimination of 5F-MDMB-PICA and 4F-MDMB-BINACA compounds also means that the metabolite analysis can be crucial for the investigation. Laboratories must be made aware of their presence and incorporate these SCs and their metabolites into workflows for detection and confirmation. Ester hydrolysis and oxidative defluorination products can be found in blood, urine and cerebrospinal fluid making them useful biomarkers of intake.
Assuntos
Líquidos Corporais , Canabinoides , Drogas Ilícitas , Masculino , Humanos , Adulto , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Líquidos Corporais/química , Líquidos Corporais/metabolismoRESUMO
In recent years, many new opioids, particularly fentanyl analogues, have appeared on the drug market. The extreme potency of even low doses of these compounds leads to numerous fatal poisonings. This also results in the fact that only sophisticated techniques are capable of detecting fentanyl analogues at concentrations that can be expected in blood. In this context, the purpose of this study was to develop a fast liquid chromatography-tandem mass spectrometry screening method for the detection of fentanyl analogues, and other new synthetic opioid receptor agonists in whole blood. Blood samples were extracted with ethyl acetate under basic conditions. The separation was achieved with the gradient of the mobile phase composition and the gradient of the flow rate in 13 minutes. The detection of all compounds was based on dynamic multiple reaction monitoring. Most of the compounds were well differentiated by their retention times and/or transitions; however, separation of some isomers has not been achieved. The validation was performed for 21 compounds. The limits of detection were in the range 0.01-0.20 ng/mL. The developed procedure enables simultaneous qualitative screening, detection and identification of 38 fentanyl analogues and five other new opioids. The method was implemented to analyze authentic samples (positive; n = 3) demonstrating its suitability for this application. The procedure can be easily expanded to include new emerging opioids, which is an indispensable advantage in the dynamically developing drug market. The developed protocol can be adopted for routine work in both forensic and clinical analytical laboratories worldwide.
Assuntos
Analgésicos Opioides/sangue , Cromatografia Líquida de Alta Pressão/métodos , Fentanila/análogos & derivados , Fentanila/sangue , Drogas Ilícitas/sangue , Programas de Rastreamento/métodos , Detecção do Abuso de Substâncias/métodos , Espectrometria de Massas em Tandem/métodos , Adulto , Evolução Fatal , Feminino , Humanos , Masculino , PolôniaRESUMO
Synthetic cathinones represent one of the largest and most abused new psychoactive substance classes, and have been involved in numerous intoxications and fatalities worldwide. Methcathinone analogues like 3-methylmethcathinone (3-MMC), 3-chloromethcathinone (3-CMC), and 4-CMC currently constitute most of synthetic cathinone seizures in Europe. Documenting their consumption in clinical/forensic casework is therefore essential to tackle this trend. Targeting metabolite markers is a go-to to document consumption in analytical toxicology, and metabolite profiling is crucial to support investigations. We sought to identify 3-CMC, 4-CMC, and 4-bromomethcathinone (4-BMC) human metabolites. The substances were incubated with human hepatocytes; incubates were screened by liquid chromatography-high-resolution tandem mass spectrometry and data were mined with Compound Discoverer (Themo Scientific). 3-CMC-positive blood, urine, and oral fluid and 4-CMC-positive urine and saliva from clinical/forensic casework were analyzed. Analyses were supported by metabolite predictions with GLORYx freeware. Twelve, ten, and ten metabolites were identified for 3-CMC, 4-CMC, and 4-BMC, respectively, with similar transformations occurring for the three cathinones. Major reactions included ketoreduction and N-demethylation. Surprisingly, predominant metabolites were produced by combination of N-demethylation and ω-carboxylation (main metabolite in 3-CMC-positive urine), and combination of ß-ketoreduction, oxidative deamination, and O-glucuronidation (main metabolite in 4-CMC-positive urine). These latter metabolites were detected in negative-ionization mode only and their non-conjugated form was not detected after glucuronide hydrolysis; this metabolic pathway was never reported for any methcathinone analogue susceptible to undergo the same transformations. These results support the need for comprehensive screening strategies in metabolite identification studies, to avoid overlooking significant metabolites and major markers of consumption.
Assuntos
Hepatócitos , Humanos , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Espectrometria de Massas em Tandem/métodos , Propiofenonas/farmacocinética , Propiofenonas/metabolismo , Cromatografia Líquida/métodos , Detecção do Abuso de Substâncias/métodos , Metanfetamina/análogos & derivados , Metanfetamina/metabolismo , Metanfetamina/administração & dosagem , Metanfetamina/farmacocinética , Psicotrópicos/farmacocinética , Psicotrópicos/metabolismo , Psicotrópicos/administração & dosagem , Metabolômica/métodos , Alcaloides/metabolismo , Drogas IlícitasRESUMO
The popularity of synthetic cannabinoids puts police sniffer dogs at risk of accidental introduction of such substances into the body. The extreme efficacy and potency of many new synthetic cannabinoids are associated with a high risk of serious poisonings and even deaths. The paper presents the toxicological findings in an intoxication of a police dog, in which a new synthetic cannabinoid ADB-BUTINACA was detected and quantified in postmortem materials. The screening analyses were performed by liquid chromatography with tandem mass spectrometry (LC-MS-MS) and liquid chromatography--quadrupole/time-of-flight mass spectrometry (LC-QTOF-MS). LC-MS-MS was also used for quantitative analyses, while LC-QTOF-MS for metabolite identification. Due to unusual matrices, the standard addition method was used for the quantitative determination of ADB-BUTINACA. The determined concentrations of ADB-BUTINACA in blood, lung, stomach, liver and kidney were 8.1 ng/mL, 6.4 ng/g, 1.5 ng/g, 1.8 ng/g and 0.4 ng/g, respectively. Apart from ADB-BUTINACA, the monohydroxylated metabolites and the dihydrodiol metabolite were detected and identified in all analyzed materials, and moreover the product of N-debutylation was found in blood and liver. The described case presents the identification and quantitation of a new synthetic cannabinoid ADB-BUTINACA in postmortem dog specimens. Although the cause of death was acute gastric dilatation, it cannot be ruled out that this process was the result of synthetic cannabinoid inhalation. Due to dogs' sensitivity to cannabinoids, ADB-BUTINACA poisoning cannot be excluded either. The described case suggests that ADB-BUTINACA elicits serious adverse effects in dogs. The article also indicates the dangers to which police dogs coming into contact with extremely potent drugs may be exposed.
Assuntos
Canabinoides , Cães Trabalhadores , Animais , Cães , Canabinoides/análise , Espectrometria de Massas , Rim/química , EstômagoRESUMO
BACKGROUND: New synthetic opioids (NSO) constitute one of the fastest-growing group of New Psychoactive Substances, which emerged on the illicit drug marker in the second half of 2000's. The most popular and the largest NSO subgroup are high potency fentanyl and its analogs. Subsequent to core-structure scheduling of fentanyl-related substances many opioids with different chemical structures are now emerging on the illicit drug market, rendering the landscape highly complex and dynamic. METHODS: PubMed, Scopus and Google Scholar were searched for appropriate articles up to December 2022. Moreover, a search for reports was conducted on Institutional websites to identify documentation published by World Health Organization, United Nations Office on Drugs and Crime, United States Drug Enforcement Administration, and European Monitoring Centre for Drugs and Drug Addiction. Only articles or reports written in English were selected. RESULTS: Non-fentanyl derived synthetic opioids, i.e., 2-benzylbenzimidazoles (nitazenes), brorphine, U-compounds, AH-7921, MT-45 and related compounds are characterized, describing them in terms of available forms, pharmacology, metabolism as well as their toxic effects. Sample procedures and analytical techniques available for detection and quantification of these compounds in biological matrices are also presented. Finally, as overdoses involving highly potent NSO may be difficult to reverse, the effectiveness of naloxone as a rescue agent in NSO overdose is discussed. CONCLUSIONS: Current review presents key information on non-fentanyl derived NSO. Access to upto-date data on substances of abuse is of great importance for clinicians, public health authorities and professionals performing analyses of biological samples.
Assuntos
Overdose de Drogas , Drogas Ilícitas , Transtornos Relacionados ao Uso de Opioides , Humanos , Analgésicos Opioides/análise , Fentanila , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Naloxona/uso terapêutico , Drogas Ilícitas/análise , Overdose de Drogas/tratamento farmacológicoRESUMO
Blood is the primary material for quantitative toxicological analysis and interpretation of the results. However, in some cases like hit-and-run, it may be collected after a long time since the incident, resulting in the complete elimination or a significant decrease in the concentrations of potentially present drugs. If the suspect was injured and bloodstains were revealed, they can become the best or sometimes, the only material to be used to prove driving under the influence of drugs. In this context, the aim of this work was to develop a simple procedure that would allow for the estimation of drug concentrations in forensic bloodstains of unknown volume. In this work endogenous amino acids: valine and leucine were used to determine the unknown volume of blood from which the stain was formed. In order to isolate the analytes from bloodstains on different surfaces (plastic and cotton) the elution mixture consisted of an acetonitrile: water (60:40) and sodium chloride (0.9%) was used. The developed protocol was tested on 32 authentic forensic samples (mostly cases of people driving under the influence of amphetamine). The results of bloodstains analyses were compared with the results of whole blood analyses. The accuracy was in the range from -87.7 to +471.0%. However, for most of the cases, more accurate results were obtained. The differences between amphetamine values estimated from bloodstains and determined from whole blood were analysed using the Bland-Altman difference plots that revealed significant agreement. The variables concentrations estimated from bloodstains and concentrations calculated from whole blood were found to be strongly correlated. The Pearson correlation coefficients were: for plastic r(29) = 0.85 and for cotton r(25) = 0.91. This is the first work in which quantitative analyses of drugs in bloodstains have been attempted. A special protocol was developed for this purpose. The conducted research indicates that estimation of the concentration of drugs in bloodstains from the blood of an unknown volume is possible. The developed protocol has been extensively tested on authentic forensic samples and the obtained results were successfully compared with drug concentrations determined in whole blood. Nevertheless, the proposed method of estimating drug concentrations in bloodstains is characterized by many disadvantages, and the determined values should be treated with great caution, at best as estimates.
Assuntos
Manchas de Sangue , Humanos , Medicina Legal/métodos , Têxteis , Anfetaminas , PlásticosRESUMO
INTRODUCTION: Synthetic cannabinoids (SCs) are the largest and most diverse group of new psychoactive substances. Their influence on organism is unpredictable and often lead to intoxications, including fatal poisonings. The interpretation of blood concentrations of detected SC although complicated, can help to determine the effects of an administered drug. The interpretation of one's own results usually requires a comparison to previously published cases, therefore, a referenced compilation of concentration ranges would be useful. MATERIAL AND METHODS: The data collection was based on a search of PubMed and Google search engine. All the available data from articles and reports where SCs concentrations have been measured in whole blood, serum or plasma were included in the data analysis. RESULTS: Presented table lists the observed concentrations in fatal and non-fatal cases involving 65 SCs. A reference list with original papers has been added for each compound, which makes it easy to find the source data. CONCLUSION: The observed concentrations of SCs vary widely and often have overlapping ranges for fatal and non-fatal cases. Conclusions regarding the cause of death are difficult based upon the concentrations alone and should include knowledge of the clinical situation in each case.
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Canabinoides/sangue , Canabinoides/intoxicação , Overdose de Drogas/sangue , Overdose de Drogas/mortalidade , Humanos , Valores de ReferênciaRESUMO
INTRODUCTION: Synthetic cathinones are the second most frequently seized group of new psychoactive substances. They are sold as replacements for controlled stimulants such as amphetamine, cocaine and MDMA. Synthetic cathinones are often determined in biological material collected from both living people and fatally intoxicated with these substances. The interpretation of analytical results usually requires a comparison to previously published cases, therefore, a referenced compilation of concentration ranges would be useful. MATERIAL AND METHODS: Data collection was based on a search of PubMed and Google search engine. All the available data from articles where synthetic cathinones concentrations have been measured in whole blood, serum or plasma were included in the data analysis. RESULTS: Presented table lists the observed concentrations in fatal and non-fatal cases involving 47 synthetic cathinones. A reference list with original papers has been added for each compound, which makes it easy to find the source data. CONCLUSION: Conclusions regarding cause of death should be based upon the concentrations and knowledge of the clinical situation. Where there is clinical suspicion of death due to synthetic cathinones, postmortem blood concentrations >1 µg/mL (in person without developed tolerance) can be cautiously considered as lethal concentrations, however the exact ranges cannot be established.
Assuntos
Alcaloides/sangue , Alcaloides/intoxicação , HumanosRESUMO
The use of novel synthetic opioids as recreational drugs has become a public health concern as they are implicated in numerous fatal intoxications across the world. Synthetic opioids have played a major role in the United States opioid crisis and may contribute to a similar opioid epidemic in Europe. The most prominent group of designer opioids consists of fentanyl and its analogues. At present, carfentanil is the most dangerous fentanyl derivative. It was recently detected as an adulterant to other illicit drugs and counterfeit pharmaceuticals, contributing to life-threatening hospital admissions and fatalities. Toxic exposure to carfentanil typically occurs through injection, insufflation or inhalation. Carfentanil produces similar pharmacotoxicological effects to other opioids. However, due to its extraordinary potency, reversing carfentanil-induced severe and recurring respiratory depression requires administration of multiple or higher than standard doses of naloxone. Toxicological reports indicate that carfentanil use is strongly connected to polydrug use. Detection of carfentanil requires specific and sensitive analytical methods that are not commonly available in hospitals. Since abuse of carfentanil is an emerging problem, particularly in the United States, there is an urgent need to develop new techniques for rapid determination of intoxication evoked by this drug as well as new treatment regimens for effective overdose maintenance. This review presents current knowledge on pharmacological activity of carfentanil, prevalence and patterns of use, and analytical methods of its detection. Special emphasis is given to carfentanil-related non-fatal and lethal overdose cases.
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Analgésicos Opioides/efeitos adversos , Fentanila/análogos & derivados , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/farmacologia , Cromatografia Líquida , Contaminação de Medicamentos , Overdose de Drogas , Fentanila/efeitos adversos , Fentanila/farmacologia , Toxicologia Forense , Humanos , Espectrometria de Massas , Naloxona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Insuficiência Respiratória/induzido quimicamenteRESUMO
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-HT2A and 5-HT2C receptors (Ki values in low nanomolar range) with more than 1000-fold selectivity for 5-HT2A compared with 5-HT1A. They display higher affinity for 5-HT2A receptors than their 2C counterparts and have markedly lower affinity, potency, and efficacy at the 5-HT2B receptor compared to 5-HT2A or 5-HT2C. 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 non-fatal 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.
RESUMO
INTRODUCTION: Cathinones are currently the second largest and the second most frequently seized group of new psychoactive substances (NPS). One of the most recent synthetic cathinones that has appeared on the 'legal highs' market is alpha-pyrrolidinoisohexanophenone (α-PiHP). CASE HISTORY: An 18-year-old man was found dead in an apartment. The autopsy materials were collected for toxicological analyses. METHODS: The quantitative analyses were carried out by LC-MS/MS. RESULTS: α-PiHP was detected and quantified in all post-mortem materials except the hair. The determined concentrations of the compound in the blood, urine and bile were 69â¯ng/mL, 2072â¯ng/mL, and 341â¯ng/mL respectively. The concentrations of α-PiHP in solid tissues were in the range of 7-478â¯ng/g. 4-Chloromethcathinone (4-CMC), N-ethylhexedrone, benzoylecgonine and 3,4-methylenedioxymethamphetamine (MDMA) were also detected in some materials. DISCUSSION: No cases presenting concentrations of α-PiHP in biological materials have been reported so far. Due to the similarity of structures and the reported dosages, an attempt to compare the concentrations of α-PVP and α-PHP has been made. In the described case, functional death through intoxication of α-PiHP was accepted as the final cause of death. The other detected substances did not contribute to death due to their very likely distant administration. CONCLUSION: α-PiHP is another new synthetic cathinone that is a danger to the life of users. The described fatal intoxication case presents the concentrations of α-PiHP in post-mortem materials. This data could be valuable for further interpretation of other results from toxicological analyses in cases where the use of α-PiHP is suspected.
Assuntos
Medicina Legal , Pirrolidinas/intoxicação , Adolescente , Cromatografia Líquida/métodos , Humanos , Masculino , Pirrolidinas/análise , Espectrometria de Massas em Tandem/métodosRESUMO
INTRODUCTION: Although there is an observed decline in the number of new psychoactive substances entering the drug market, this phenomenon is still a significant public health problem. Synthetic cathinones are the second largest group of new substances and currently belong to the most frequently confiscated. Their availability and prevalence cause that they are often abused. Because of this, they should be detected and determined as part of routine toxicological screening in materials collected from both the living and cadavers. Recent reports indicate, however, that some of them are unstable in biological matrices. The aim of the study was the systematic evaluation of changes in concentrations of synthetic cathinones in whole blood and urine samples stored long-term under different temperature conditions. MATERIAL AND METHODS: The study involved 17 compounds that were added to blood and urine to obtain a concentration of 100ng/mL. The material was stored at room temperature (24°C), refrigerated (5°C) and frozen (-26°C) for six months. The extraction was initially performed daily, and then at 1-4week intervals. The analyses were carried out using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The calculated drugs content over time allowed the estimation of the half-life and total degradation time of the tested compounds. RESULTS: The conducted research indicated that the temperature and matrix have a significant influence on the stability of cathinones, as well as the pH. Significant decreases in the concentrations of some analytes were observed within just several dozen hours of storage at room temperature. The most unstable was 4-chloromethcathinone (4-CMC), for which the half-life in blood was determined to be <1day at room temperature, 4days in the refrigerator and 32days in the freezer. On the other hand, the most stable were 3,4-methylenedioxy derivatives (pentylone, eutylone, butylone and dibutylone). Significant differences in the rate of breakdown of cathinones in blood and urine stored at room temperature were observed. The pH of the sample had a great impact on the stability of cathinones, especially in urine. CONCLUSION: Many synthetic cathinones are unstable in biological materials. Changes in concentrations are observed even in recommended manner stored samples. This may lead to a lower calculated concentration than when the material was collected or at the time of death. Total decomposition of the substance is also possible. Obtained results emphasize the importance of proper storage of samples and the possibility of pre-analytical changes in concentrations, in particular during routine material transportation.
Assuntos
Alcaloides/sangue , Alcaloides/urina , Estabilidade de Medicamentos , Psicotrópicos/sangue , Psicotrópicos/urina , Alcaloides/química , Cromatografia Líquida , Meia-Vida , Humanos , Concentração de Íons de Hidrogênio , Psicotrópicos/química , Manejo de Espécimes , Medicamentos Sintéticos/análise , Medicamentos Sintéticos/química , Espectrometria de Massas em Tandem , TemperaturaRESUMO
The increase in the number of new substances appearing on the drug market has been observed in the 1980s and 1990s of the last century, when many phenethylamine and tryptamine derivatives entered the market. However, the phenomenon of mass marketing of new designer stimulants (being the components of so-called "legal highs") began to develop since 2006 in Europe, and it was something new. Since then, the number of stimulants introduced on the drug market is growing regularly, rapidly, and intensively. Such a situation creates a need for comprehensive screening methods for detection of these drugs in biological specimens. The fast and simple liquid chromatography-tandem mass spectrometry qualitative screening procedure presented here is designed to detect and identify a wide range of designer stimulants in the blood. The assay has wide applicability for rapid screening of new stimulants in forensic or clinical samples. The procedure can be easily modified for additional novel psychoactive substances.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacocinética , Cromatografia Líquida , Monitoramento de Medicamentos , Espectrometria de Massas em Tandem , Estimulantes do Sistema Nervoso Central/sangue , Cromatografia Líquida/métodos , Monitoramento de Medicamentos/métodos , Humanos , Detecção do Abuso de Substâncias/métodos , Espectrometria de Massas em Tandem/métodosRESUMO
INTRODUCTION: The second largest group of new drugs monitored by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) is synthetic cathinones. Substances that are controlled by the law are immediately replaced by new uncontrolled derivatives that cause constant and dynamic changes on the drug market. Some of the most recent synthetic cathinones that have appeared on the "legal highs" market are 3,4-methylenedioxy-α-pyrrolidinohexanophenone (3,4-MDPHP) and α-pyrrolidinohexanophenone (α-PHP). CASE HISTORY: A 21-year-old woman in the 36th week of pregnancy presented with psychomotor agitation. Fetal demise was demonstrated and a caesarean delivery performed. METHODS: The analyses were carried out by liquid chromatography with mass spectrometry (LC-MS/MS). The analytes were isolated from the biological material by liquid-liquid extraction with n-butyl chloride. RESULTS: 3,4-MDPHP and α-PHP were detected and quantified in both the fetus' and the mothers blood, as well as in the mothers urine samples. The determined concentrations of 3,4-MDPHP and α-PHP were, 76 ng/mL and 12 ng/mL in the fetal blood sample, 16 ng/mL and traces in the mothers blood, and 697 mg/mL and 136 ng/mL in the mothers urine, respectively. DISCUSSION: The presented case demonstrates that 3,4-MDPHP and α-PHP transfers from maternal blood to fetal blood. Blood concentrations of these compounds were higher in the fetus than in the mother. Based on the known effects of these substances and the patient's presentation and clinical course, it would seem that these substances contributed to the fetal death. CONCLUSIONS: The detected substances transfer from maternal to fetal circulation, and synthetic cathinone blood concentration can be higher in the fetus than in the mother. This along with the fact immature metabolic ability makes a fetus more vulnerable to cathinones intoxication than adults.
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Morte Fetal/etiologia , Drogas Ilícitas/toxicidade , Pirrolidinas/toxicidade , Acatisia Induzida por Medicamentos/etiologia , Feminino , Sangue Fetal/química , Humanos , Drogas Ilícitas/sangue , Gravidez , Complicações na Gravidez/induzido quimicamente , Pirrolidinas/sangue , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto JovemRESUMO
Introduction: Synthetic cannabinoids are currently the largest group of new psychoactive substances. Those that have been subjected to legal control are replaced by newer uncontrolled substances, which causes constant and dynamic changes to the drug market. Some of the most recent synthetic cannabinoids that have appeared on the "legal highs" market are AMB-FUBINACA and EMB-FUBINACA. Case history: A 27-year-old man was found dead on a bed in an apartment. At autopsy, congestion of internal organs, pulmonary oedema and left-sided pleural adhesions were found. The medical examiner concluded that the man died due to acute respiratory failure. The autopsy materials (blood, urine, liver, kidney, stomach, intestine, lung and brain) were collected for further toxicological analyses. Methods: The synthetic cannabinoids AMB-FUBINACA and EMB-FUBINACA were isolated from autopsy materials by precipitation with acetonitrile. The quantitative analyses were carried out by LC-MS/MS. Results: AMB-FUBINACA and EMB-FUBINACA were detected and quantified in all post-mortem materials except the blood. The determined concentrations of these compounds in solid tissues were in the range of 0.2-0.9 ng/g and 0.2-3.5 ng/g. The highest concentrations of AMB-FUBINACA and EMB-FUBINACA were revealed in the stomach content (5.8 and 36.2 ng/mL, respectively). Discussion: The presented case demonstrates that even in cases of fatalities, it is possible that the parent substance will not be present in the blood, while being present in other autopsy materials. The determined concentrations of the compounds may indicate oral administration of synthetic cannabinoids. It can also be assumed that AMB-FUBINACA and EMB-FUBINACA probably contributed to death. Conclusion: The presented case shows that synthetic cannabinoids can be undetected in the blood of even seriously or fatally intoxicated people. This situation means that the analysis of only blood samples may not confirm poisoning. The presented case also suggests that AMB-FUBINACA and EMB-FUBINACA use is dangerous to health and may lead to fatal intoxication.
Assuntos
Indazóis/intoxicação , Transtornos Relacionados ao Uso de Substâncias/etiologia , Valina/análogos & derivados , Adulto , Autopsia , Evolução Fatal , Humanos , Indazóis/análise , Lidocaína/sangue , Lorazepam/sangue , Masculino , Valina/análise , Valina/intoxicaçãoRESUMO
Urine tests are the commonly accepted methods to control abstinence and adherence to treatment of patients who undergo methadone maintenance treatment (MMT). Depending on various national guidelines and accessibility of techniques, only selected psychoactive substances are routinely tested in urine of MMT patients. In general, they belong to the few groups of compounds: THC, cocaine, amphetamines, opiates, PCP and benzodiazepines. It is, however, well known that patients enrolled in such replacement programmes take psychoactive substances that are not routinely detected by the toxicology laboratories, to escape unexpected tests. Here, we report semiquantitative detection of legal highs taken by the MMT patient, using high-pressure liquid chromatography coupled to the flowing atmospheric pressure afterglow ion source (LC-FAPA-MS). To demonstrate effectivity of this technique, the data were confirmed by quantitative analysis using LC-ESI-MS/MS. In the analysed sample of MMT patient, a mixture of psychoactive compounds was found, namely 3-MMC (3-methylmethcathinone), pentedrone and methcathinone and determined at the concentrations of 670; 50 and 0.2 µg/mL, respectively. Such fast analytical technique may be useful for the efficient control of substances taken intentionally by MMT patients.
Assuntos
Metadona/uso terapêutico , Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Psicotrópicos/urina , Detecção do Abuso de Substâncias/métodos , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Humanos , Limite de Detecção , Metanfetamina/análogos & derivados , Metanfetamina/urina , Metilaminas/urina , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/urina , Cooperação do Paciente , Pentanonas/urina , Propiofenonas/urina , Espectrometria de Massas em Tandem/métodosRESUMO
PURPOSE: In recent years, many synthetic cannabinoids (SCs) have appeared on the drug market. Despite the increasing number of SCs, there are few comprehensive screening methods for their detection in biological specimens. In this context, the purpose of this study was to develop a fast and simple liquid chromatography-tandem mass spectrometry screening procedure for detection and identification of SCs in whole blood. METHODS: The elaborated qualitative screening method allows the simultaneous detection and identification of 72 compounds from different chemical groups: naphthoylindoles, naphthoylindazoles, benzoylindoles, phenylacetylindoles, tetramethylcyclopropylindoles, indole-3-carboxylic acid esters, indole-3-carboxylic acid amides, indazole-3-carboxylic acid amides, and others. Whole-blood samples (0.2 mL) were precipitated with acetonitrile (0.6 mL). The separation was achieved with the gradient of the mobile phase composition (0.1% formic acid in acetonitrile and 0.1% formic acid in water) and the gradient of the flow rate (0.5-0.8 mL/min) in 16 min. Detection of all compounds was based on dynamic multiple reaction monitoring. RESULTS: Mass spectrometer parameters for all compounds were presented. All of the compounds were well-separated by their retention times and/or transitions. The limits of detection (LODs) for 50 compounds were in the range 0.01-0.48 ng/mL. CONCLUSIONS: Estimated LODs make this assay suitable for the analysis of biological material. The procedure can be easily expanded for more substances, which is an indispensable advantage in the dynamically developing drug market. It can have wide application in various analytical forensic and clinical laboratories.
RESUMO
Cathinone derivatives are notorious but still weakly characterized molecules, known mainly as components of the designer and illicit drugs. The knowledge on their acidity is scarce and incomplete, therefore, we decided to determine the pKa values for six of them: 2-methylmethcathinone, 3-methylmethcathinone, 4-methylmethcathinone, α-pyrrolidinovalerophenone, methylenedioxypyrovalerone and ephedrone. For that purpose we employed capillary electrophoresis, which is known for its accurateness in comparison to other analytical techniques. We used and compared two methodologically different approaches. The standard method relied on measuring electrophoretic mobility across the broad pH range and fitting the sigmoidal function. The obtained pKa values were in the range 8.59-9.10, thus these molecules remain mostly protonated and positively ionized in the physiological conditions. The alternative two-values (TVM) and one-value methods (OVM), proposed by us previously, have been used herein for the first time to the cationic molecules. TVM enables estimation of pKa using only two electrophoretic mobility values, referring to the total and partial ionization. OVM requires only a single measurement because mobility of ion is predicted theoretically. Both TVM and OVM yielded only a small deviation of pKa from the standard approach, averagely 0.07-0.09pH unit. Two important issues have also been addressed: the potential of a maximally fast calculation method using no repetition at the given pH, and the accuracy of method with regard to pH attributed to partial ionization. As a whole, the analytical potential of the TVM/OVM approach seems to be huge and invaluable for fast pKa screening/estimation.