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Identifying possible new biological activities of psychoactive substances belonging to various chemical classes may lead to a better understanding of their mode of action and side effects. We report here that amines structurally related to amphetamine, a widely used psychoactive substance, such as amphetamine, methamphetamine, phentermine, mephentermine, and chlorphenteramine, potently activate several carbonic anhydrase (CA, EC 4.2.1.1) isoforms involved in important physiological functions. Of the 11 investigated human (h) isoforms, the widespread hCA I and II, the secreted hCA VI, as well as the cytosolic hCA XIII, and membrane-bound hCA IX and XIV were poorly activated by these amines, whereas the extracellular hCA IV, the mitochondrial enzymes hCA VA/VB, the cytosolic hCA VII, and the transmembrane isoform hCA XII were potently activated. Some of these enzymes are abundant in the brain, raising the possibility that some of the cognitive effects of such psychoactive substances might be related to their activation of these enzymes.
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Anfetamina/clasificación , Anfetamina/farmacología , Encéfalo/enzimología , Anhidrasas Carbónicas/metabolismo , Psicotrópicos/clasificación , Psicotrópicos/farmacología , Anfetamina/química , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Humanos , Isoenzimas/metabolismo , Modelos Moleculares , Estructura Molecular , Psicotrópicos/química , Relación Estructura-ActividadRESUMEN
Identification of new psychoactive substances (NPS) in biological and non-biological samples represents a hard challenge for forensic toxicologists. Their great chemical variety and the speed with which new NPS are synthesised and spread make stringent the need of advanced tools for their detection based on multidisciplinary approaches. For this reason, in August 2016, the "Unit of Research and Innovation in Forensic Toxicology and Neuroscience of Addiction" (U.R.I.To.N.) was founded by the Forensic Toxicology Division of the University of Florence. In this Research Unit, various professionals (i.e. forensic toxicologists, chemists, physicians) collaborate to study all the aspects of drugs of abuse, especially NPS. Herein, we describe the multidisciplinary approach comprising liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), gas chromatography hyphenated to mass spectrometry (GC-MS) and solution nuclear magnetic resonance analysis that allowed the identification of three NPS such as 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 2-amino-1-(4-bromo-2,5-dimethoxyphenyl)ethan-1-one (bk-2C-B), and 3-(2-aminopropyl)indole (α-methyltryptamine) in seized materials.
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Psicotrópicos/análisis , Cromatografía Liquida , Espectroscopía de Resonancia Magnética , Estructura Molecular , Psicotrópicos/síntesis química , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Clinical reliability of self-reported data for alcohol, caffeine, and nicotine consumptions is lacking, particularly in adolescents. OBJECTIVES: To compare a self-report questionnaire and hair analysis to assess the reliability and effectiveness of the self-report. METHODS: A cross-sectional study on 14-15-year-old Italian students (n = 874, 38% males, 62% females) was performed comparing self-reported data to hair analysis. The latter quantified hair concentrations of caffeine, nicotine, cotinine, ethyl glucuronide (EtG), and fatty acid ethyl esters (FAEEs) using mass spectrometry. RESULTS: Concordance between self-report and hair testing ranged from good to poor across substances and levels of use: poor for heavy alcohol intake (EtG: k = 0.36, 20 positive cases by hair analysis, false negative by self-report, 2.3% of total sample; FAEE k = 0.31, 25 positive cases, 2.9% of total sample); fair to poor for active smokers (k = 0.40, 125 positive cases, 14.3% of total sample); and moderate for caffeine (k = 0.57, 56 positive cases, 6.4% of total sample). CONCLUSIONS: Epidemiological studies on alcohol, caffeine, and nicotine consumption in adolescents may benefit from the inclusion of toxicological analysis on hair samples to overcome the under-reporting phenomenon of questionnaires and detect more cases of problematic substance use.
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Cafeína/análisis , Cabello/química , Nicotina/análisis , Detección de Abuso de Sustancias/métodos , Adolescente , Consumo de Bebidas Alcohólicas/metabolismo , Cafeína/administración & dosificación , Cotinina/análisis , Estudios Transversales , Reacciones Falso Negativas , Femenino , Glucuronatos/análisis , Humanos , Italia , Masculino , Espectrometría de Masas/métodos , Nicotina/administración & dosificación , Reproducibilidad de los Resultados , Autoinforme , Fumar/metabolismo , Encuestas y CuestionariosRESUMEN
Fatty acid ethyl esters (FAEEs) and ethyl-glucuronide (EtG) in meconium have been widely studied as biomarkers of maternal alcohol consumption during pregnancy. Many analytical approaches have been proposed for their analysis, mostly consisting of separated extraction procedures requiring the use of two meconium aliquots. This study aimed to validate a new analytical procedure for the simultaneous extraction of FAEEs and EtG from a meconium aliquot through a single solid-phase extraction (SPE) applied to 242 anonymized samples of meconium. Targeted FAEEs were: ethyl-myristate (Myr), ethyl-palmitate (Pal), ethyl-oleate (Ole) and ethyl-stearate (Ste). Two hundred milligrams of meconium was sonicated with acetonitrile, and a single SPE performed by means of aminopropyl columns. FAEEs were eluted with hexane, followed by EtG elution with water. Both the mixtures were dried, recovered, and analyzed by liquid chromatography-tandem mass spectrometry using C8 (FAEEs) and C18 (EtG) columns. Transitions were: m/z 257 â 57,88, Myr; m/z 262 â 57,88, Myr-d5; m/z 285 â 57, 72, Pal; m/z 290 â 57,258, Pal-d5; m/z 311 â 72,114, Ole; m/z 316 â 72,265, Ole-d5; m/z 257 â 57,72 Ste; m/z 318 â 57,286, Ste-d5; m/z 221 â 75,85, EtG; m/z 226 â 75,85, EtG-d5. Lower limit of quantification range was 10-15 ng/g for FAEEs and 10 ng/g for EtG. Linearity was evaluated for different concentration ranges; the mean coefficients of determination (R (2)) were above 0.9961. Precision and accuracy for FAEEs and EtG were consistently ≤20 % and ±20 %, respectively. Ion suppression was observed for all the analytes. Matrix effect did not significantly affect the analyses. Recovery efficiency was 93 % for EtG and 75-85 % for FAEEs.
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Cromatografía Liquida/métodos , Ácidos Grasos/análisis , Glucuronatos/análisis , Meconio/química , Espectrometría de Masas en Tándem/métodos , Ésteres , Límite de Detección , Reproducibilidad de los ResultadosRESUMEN
Propofol is a low-polarity, volatile molecule that is difficult for an electrospray ion source (ESI) to ionize in either negative ion mode (NIM) or positive ion mode (PIM), which hampers its detection via liquid chromatography-mass spectrometry. The aim of the present study was to use a new derivatization agent to improve ionization efficiency and to develop an efficient liquid chromatography-multiple mass spectrometry (LC-MS/MS) determination of propofol in urine and blood, taking advantage of an electrophilic aromatic substitution. An azo-coupling reaction with a diazonium salt from aniline was performed to introduce a protonation site into the molecule. The diazonium salt was generated by aniline in water solution by HCl and sodium nitrite; derivatization was achieved by stirring a mixture of the diazonium salt and propofol in sodium hydroxide solution for 30 min below 5 °C. A liquid-liquid extraction with dichloromethane and ethyl acetate was performed to obtain the azo derivative (molecular composition: C18H22ON2; molecular weight: 282 Da) in high yield. The compound provided very high ionization yields in both PIM and NIM ESI, and the protonated or deprotonated molecule gave intense signals. The transitions m/z 283 â 77, 241 and m/z 281 â 176, 161 were chosen for the PIM and NIM, respectively, in order to develop quantitative methods of detecting propofol in urine and blood via triple-quadrupole LC-MS/MS. These methods proved to be highly sensitive, with limits of quantification of 0.4 pg/mL and 0.1 ng/mL obtained in the NIM when analyzing 1 mL of urine and 100 µL of blood, respectively.
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Cromatografía Liquida , Propofol/sangre , Propofol/orina , Espectrometría de Masas en Tándem , Compuestos Azo/química , Toxicología Forense/métodos , Humanos , Concentración de Iones de Hidrógeno , Iones , Modelos Químicos , Propofol/química , Protones , Control de Calidad , Análisis de Regresión , Reproducibilidad de los Resultados , Sales (Química)/química , Sensibilidad y Especificidad , TemperaturaRESUMEN
MDPHP is a synthetic cathinone (SC) belonging to α-pyrrolidinophenone derivatives. It is a central nervous system stimulant and may induce hallucinations, paranoia, tachycardia, hypertension, chest pain, and rhabdomyolysis. In literature, a few cases of intoxication have been reported. In the present study, 17 cases of MDPHP intake were described including the analytical findings and clinical manifestations. MDPHP was quantified by liquid chromatography-tandem mass spectrometry in blood (range 1.26-73.30 ng/mL) and urine (range 19.31-8769.64 ng/mL) samples. In three cases the presence of α-PHP was observed. In one case, MDPHP was the only detected substance. Concomitant use of MDPHP with other substances, particularly psychostimulants, was common and it was difficult to describe the peculiar clinical characteristics of this SC. Most of the symptoms overlapped those expected, some of them were unusual and all of them particularly severe thus inducing the research of NPS in laboratory tests. We demonstrated the presence of psychiatric, neurological, and respiratory symptoms, as well as the possible presence of rhabdomyolysis and cardiotoxicity associated with the use of MDPHP. ED admissions were also more frequent in patients with addiction problems. In some cases, MDPHP intake required intensive supportive care. A multidisciplinary approach, including specialist consultation, is recommended for patients showing challenging features. Moreover, we demonstrated that the adoption of advanced analytical techniques, i.e., liquid chromatography-tandem mass spectrometry, is necessary to detect these molecules. Further studies are needed to understand MDPHP intake patterns and associated symptoms. It is essential to raise awareness in addiction treatment centers and among potential users, especially young people, and chemsex addicted.
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Estimulantes del Sistema Nervioso Central , Rabdomiólisis , Humanos , Adolescente , Cathinona Sintética , Espectrometría de Masas , Cromatografía LiquidaRESUMEN
Evaluation of Cannabis consumption is required for many purposes (i.e., workplace drug testing and driving license renewal). Hair analysis represents the most adopted and reliable approach for the investigation of repeated or chronic exposure to Cannabis. The main markers are the Δ9-tetrahydrocannabinol (THC) and its main metabolite, 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), as stated by the Society of Hair Testing (SoHT) and the European Workplace Drug Testing Society (EWDTS). In this paper we presented an observational study on the hair concentrations of THC and THC-COOH and influences due to age, gender, consumption habits, and hair features. Data were collected from analysis of scalp hair samples (3-cm proximal segment) provided by subjects tested for THC consumption for personal purposes (i.e., workplace drug testing, personal use proving). The subjects provided an informed consent and a short questionnaire. A new analytical method was previously developed and then adopted. It consisted in a hydrolysis (1 mL of 1 M NaOH at 65 °C, 20 min) and a liquid-liquid extraction (with hexane/ethyl acetate,90/10, v/v in presence of 1.5 mL of H2SO4 1 M) of 25 mg of hair. A liquid chromatograph - tandem mass spectrometer (LC-MS/MS) equipped with a C18 column was used. The acquisition was in multiple reaction monitoring for the following transitions: 315â259, 193 m/z, for THC; 318â196, 123 m/z, for THC-d3; 345â299, 193 m/z for THC-COOH; 348â196, 302 m/z for THC-COOH-d3. Correlation between THC and THC-COOH hair concentrations was analyzed by Spearman's rank correlation coefficient. In order to study the influences of several variables, a new value, Sqrt(THC*THCCOOH), was adopted. Its effectiveness and reliability were proved by the Principal Component Analysis. Relationships between the Sqrt(THC*THCCOOH) and the variables were studied through the Stepwise regression (p = 0.05). The normality of data distribution was tested by the Shapiro-Wilk test. The Lower limits of quantification were 10.0 (THC) and 0.2 (THC-COOH) pg/mg. Accuracy and precision always met the acceptable criteria. Recoveries were > 78% and ion suppression was observed for both the compounds. Data from 126 hair samples were included in this study: 54 subjects(42.9%) were positive both for THC and THC-COOH; none of the samples was positive for a single substance. Concentrations ranged from 0.18 to 1.75 ng/mg (median: 0.78 ng/mg) for THC and from 0.04 to 0.85 ng/mg (median: 0.31 ng/mg) for THC-COOH. Cannabinoids levels seemed to decrease with the age, with lower amounts in the subjects aged > 40 years (p < 0.05). Also years of consumption seemed to have a significant impact on hair concentrations, as higher levels were observed in consumers from > 10 years (p = 0.013). Moreover, this study further provided evidences of a significant reduction of THC and THC-COOH in bleached hair (p = 0.042).
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Cannabis , Alucinógenos , Humanos , Adulto , Dronabinol , Cromatografía Liquida , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/métodos , Cabello/química , Detección de Abuso de Sustancias/métodosRESUMEN
The best evidence provided in the literature worldwide suggests the importance of harmonizing the investigation in drug-related fatalities. In this study, the application of a multidisciplinary approach in eight cases of drug-related deaths is presented. Although death scene findings could be highly suggestive of drug intoxication, external examination and toxicological screening test alone are insufficient. There are several variables, and it is not always easy to give the proper interpretation of the drug detection. A complete autopsy is necessary to correctly complete organ and tissues sampling for further histological and toxicological studies and obtain body fluids. The use of peripheral blood is recommended to avoid artifacts. The collection of many specimens is warranted to get more responses. The sampling aims to provide a picture of the distribution of the substance in the body. The sample and the selection of the drugs and the matrices to investigate are case-dependent. The presented diagnostic algorithm provides the coroner with all the elements to investigate drug-related deaths and cooperate with toxicologists. Toxicological forensic diagnosis is still extremely heterogeneous in regional and national contexts. Funding for method development, research, networking, facilities, and technologies improvement is mandatory to standardize the toxicological investigation.
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Ethyl glucuronide (EtG) is a non-volatile, non-oxidative, hydrophilic, and stable ethanol phase II metabolite. EtG is produced through ethanol glucuronidation by UDP-glucuronosyltransferase (UGT), a phase II enzyme. EtG can be extracted from different biological matrices, including keratin ones, such as hair or nails. The purpose of this scoping review is to describe the relationship between EtG levels in hair and some of the most common and frequent pathological conditions and verify whether different reference cut-offs in relation to various pathologies have been identified in the scientific literature. In fact, in-depth knowledge of the influence of pathologies, such as diabetes mellitus, hepatic and renal dysfunction, on EtG production and its storage in keratin matrices would allow a more appropriate interpretation of obtained data and rule out false positives or false negatives. This scoping review is based on bibliographic research carried out on PubMed regarding the quantification of EtG in hair of subjects affected by different pathological conditions. According to the scientific literature, the main and most common pathologies that can affect the concentration of EtG in hair are liver and kidney diseases and diabetes. The EtG quantification analytical data should be interpreted carefully as they may have a great impact in both forensic and clinical contexts.
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The use of illicit and non-illicit substances is widespread in suicides. The toxicological data may help in understanding the mechanism of death. This systematic review aimed to analyze autopsies related to suicides by consuming poison, focusing on the correlation between substance use and the country of origin to create an alarm bell to indicate that suicide maybe attempted and prevent it. The systematic review was conducted according to the PRISMA guidelines, with the primary objective of identifying autopsies conducted in cases of suicide by consuming poison in specific geographic areas. Significant differences in substances were observed between low-income and Western countries that confirm previous literature data. In rural areas and Asian countries, most suicides by consuming poison involve the use of pesticides, such as organophosphates and carbamates. In Western countries, illicit drugs and medically prescribed drugs are the leading cause of suicide by self-poisoning. Future research should shed light on the correlation between social, medical, and demographic characteristics and the autopsy findings in suicides by self-poisoning to highlight the risk factors and implement tailored prevention programs worldwide. Performing a complete autopsy on a suspected suicide by self-poisoning could be essential in supporting worldwide public health measures and policy makers. Therefore, complete autopsies in such cases must be vigorously promoted.
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Cognitive deficits are enduring and disabling symptoms for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. In this study, we reported the synthesis of ß-arylchalcogeno amines bearing sulfurated, selenated, and tellurated moieties (2-4) which are structurally related to amphetamine with good activation properties for Carbonic Anhydrases (CAs) isoforms present in the cortical and hippocampal brain structures (hCA IV and hCA XIV). In addition, these compounds showed selective inhibition against the Monoamine oxidase (MAO) A isoform. In vivo evaluation of two derivatives (2a and 3a) revealed procognitive effects in the object recognition and social discrimination tests. Interestingly, these compounds, despite having a similar structure to amphetamine, did not caused hypophagia or hyperlocomotion, two effects often observed following the administration of amphetamine-like drugs. In this context, ß-arylchalcogeno amines may have utility for improving the symptoms of cognitive decline associated with neurodegenerative and psychiatric diseases such as attention deficit disorder, Parkinson's disease-related cognitive dysfunction and cognitive disorders associated with depression.
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Anhidrasas Carbónicas , Humanos , Anhidrasas Carbónicas/metabolismo , Aminas/farmacología , Monoaminooxidasa , Isoformas de Proteínas , Inhibidores de Anhidrasa Carbónica/química , Relación Estructura-Actividad , Anhidrasa Carbónica IX/metabolismoRESUMEN
Endogenous nature of GHB represents a critical issue for forensic toxicologists, especially in alleged sexual assaults. Therefore, discrimination between physiologically and additional amounts from exogenous sources of such a substance must be effective and reliable in order to avoid severe misinterpretation. This study aimed to quantify the GHB baseline concentrations in chest and pubic hairs collected from 105 healthy volunteers, non-consumers of any drugs of abuse. The final scope was to investigate if these keratin matrices could represent valid alternative to scalp hair when not available. Moreover, we also evaluated the age and gender influences on the GHB baseline levels. 25 mg of hair were incubated overnight with NaOH at 56 °C. After acidification with H2SO4, the solution was liquid-liquid extracted with ethyl acetate and a trimethylsilyl derivatization was then achieved. Analysis was performed in gas chromatography-mass spectrometry in single ion monitoring mode (m/z 233, 234, 147 for GHB; m/z 239, 240 and 147 for GHB-d6). The endogenous amount in "blank" hair was estimated by the standard addition method (0.301 for chest hair and 0.235 ng/mg for pubic hair). GHB concentration ranged from 0.205 to 1.511 ng/mg for chest hair and from 0.310 to 1.913 ng/mg for pubic hair. These values were consistent with previous studies on scalp hair and on pubic hair. Unfortunately, research on chest hair is not available in literature. T-Test and Linear Regression highlighted no statistically significant differences for the two matrices and for all age/gender sub-groups. However, further studies are required to estimate a reliable cut-off value for these keratin matrices. For the first time, we demonstrated the suitability of chest and pubic hair to detect endogenous levels of GHB.
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Cabello/metabolismo , Oxibato de Sodio/metabolismo , Adulto , Factores de Edad , Femenino , Medicina Legal , Cromatografía de Gases y Espectrometría de Masas , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Factores SexualesRESUMEN
Quetiapine is an atypical antipsychotic drug used to treat bipolar disorder, schizophrenia, and major depressive disorder. Although several studies describe the adverse effects of intoxication with Quetiapine, only a few report an extreme overdose without comedications that lead to a life threat. We present a case of a 75-year-old male who tried to attempt suicide by ingesting 28 g of Quetiapine. During the management in the emergency department, both serum and urine samples were collected, allowing a complete pharmacokinetic analysis to be conducted, from the admission to the discharge.
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Gamma-hydroxybutyric acid (GHB), usually reported as rape drug in drug-facilitated sexual assaults (DFSA), is an endogenous substance in human body and is also found in many beverages. This may lead to data misinterpretation in forensic cases. Herein, we aimed to collect evidence about natural GHB presence in 13 energy drinks (ED). After a liquid-liquid extraction with acidic ethyl acetate, samples were derivatized with BSTFA 1% TMCS. Analyses were carried out by a GC-MS system in SIM mode (GHB, 233, 234, 143 and 147 m/z; GHB-d6, 239, 240, 120 and 206 m/z). GHB was present in all the samples at very low concentrations ranging from 98 to 197 ng/mL. Thus, GHB presence in ED is not exclusively related to exogenous addition. Since the GHB levels are far lower than the minimum active dose (i.e., 0.5 g), it is not expected to induce any effect.
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Bebidas Energéticas/análisis , Hidroxibutiratos/análisis , Medicina Legal , Cromatografía de Gases y Espectrometría de Masas , Cabello/química , Detección de Abuso de SustanciasRESUMEN
Local anaesthetics (LAs) are commonly used in surgery, especially in dentistry. They cause a transitory inhibition of nerve signal due to the blockade of the voltage-gated sodium channels. LAs are administrated alone or with vasoconstriction agents, such as adrenaline. Toxicity of LAs is associated to neurological and cardiovascular alterations. Tachycardia, arrhythmia, tremors, tonic-clonic seizure and respiratory depression (at high doses) are the main symptoms of intoxication by LAs. Lidocaine, articaine and mepivacaine are among the most used anaesthetics. This study aimed to fully validated a new method for the simultaneous detection of articaine and mepivacaine in whole blood. Sample treatment consisted in a liquid-liquid extraction with phosphate buffer (pH 8, 0.1 M) and ethyl-acetate. Analysis was performed by liquid chromatography-tandem mass spectrometry in multiple reaction monitoring mode (transitions: articaine, 285â8658 m/z; mepivacaine, 247â9870 m/z; lidocaine - internal standard -, 235â8658 m/z). The method proved to be highly sensitive with limit of quantifications for articaine and mepivacaine of 0.8 and 0.1 ng/mL, respectively. Accuracy and precision were always within the acceptance criteria. The new procedure was also successfully applied to a preliminary pharmacokinetics study.
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Anestésicos Locales/análisis , Carticaína/análisis , Cromatografía Liquida/métodos , Mepivacaína/análisis , Anestésicos Locales/farmacocinética , Carticaína/farmacocinética , Femenino , Humanos , Extracción Líquido-Líquido , Masculino , Mepivacaína/farmacocinética , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/métodosRESUMEN
In last years, international and national Institutions have been completely focused on the new psychoactive substances (NPS) phenomenon. Many contrast policies have been planned in order to control their spread. Even scientific entities, such as our Forensic Toxicology Division, have spent time and resources for NPS identification in biological (from clinical and forensic caseworks) and non-biological (seized material) samples. Last reports show a low prevalence of NPS across the Europe and Italy, while the classical drugs are still the main cause of drug-related deaths. In particular, a worrisome datum is represented by the increasing number of deaths due to heroin. Seen these statistics, is the NPS phenomenon overestimated? Is the interest in classical drugs decreased? Were we diverted by NPS?
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Tráfico de Drogas/tendencias , Psicotrópicos/efectos adversos , Trastornos Relacionados con Sustancias/epidemiología , Drogas de Diseño/efectos adversos , Toxicología Forense , Humanos , Drogas Ilícitas/efectos adversosRESUMEN
Objective: Driving under the influence (DUI) of psychotropic substances is a serious and widespread problem in road safety. All countries try to reduce the impact with legislative controls over the criteria to regain a driver's license after suspension. In many European countries there are mandatory clinical and toxicological examinations required before a license is regranted. In Italy, individuals convicted of driving under the influence of drugs and/or alcohol must undergo a mandatory medico-legal and forensic toxicological examination prior to regranting of a license. This article reports on the prevalence, trends, and implications of psychotropic substances detected in more than 5,000 subjects submitted to driving license reissuance in the period 2011-2016. Methods: The study involved taking a clinical history, medical examination, and toxicological analysis of both urine and hair samples. Results: There was no change in the prevalence of psychoactive substances in the period 2011-2016. Cocaine was found most often (60%), followed by cannabinoids (15%) and opiates (9%). Methadone and amphetamine stimulants accounted for less than 5% each. Benzodiazepines were present in 15% of samples throughout the period. Conclusion: Cocaine and cannabinoids were the most used substances in the analyzed population, alone and in combination. Benzodiazepines were the most commonly detected prescription medication, raising questions about prescribed medication and driving risk that are not addressed by current legislation.
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Conducción de Automóvil/legislación & jurisprudencia , Concesión de Licencias/legislación & jurisprudencia , Psicotrópicos/aislamiento & purificación , Detección de Abuso de Sustancias/estadística & datos numéricos , Adolescente , Adulto , Anciano , Conducir bajo la Influencia/legislación & jurisprudencia , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
In this work, the physical and chemical properties of a novel zwitterionic LC stationary phase are applied to the development, validation and application of a new fast and reliable method devoted to the analysis of GHB (gamma-hydroxybutyric acid) and its relatively new discovered glucuronide metabolite in hair. The obtained sensitivity, expressed as limit of detection (LOD) and quantification (LOQ), were 0.033 and 0.10â¯ng/mg for GHB and 0.11 and 0.37â¯ng/mg, for GHB-glucuronide respectively. Linearity was assessed between LOQ and 50â¯ng/mg for both compounds. GHB and GHB-glucuronide extraction from hair matrix was maintained simple and consisted in an acidified-solvent incubation. No samples purification was required before LC-MS/MS analysis. The method was finally applied to 65 real hair sample, 60 adults and 5 children below 2â¯years old. The obtained results highlighted that GHB concentrations were in the range 0.11-0.96â¯ng/mg (average 0.38⯱â¯0.25â¯ng/mg) in 44 cases (68%) while in 21 samples GHB concentrations were in the range between LOD and LOQ (0.033-0.1â¯ng/mg). GHB-glucuronide was detected in few samples (n. 3) at levels below LOQ. The interest on these molecules relies on the fact that GHB is both a naturally occurring inhibitory neurotransmitter in the central nervous system and an illicit drug often experienced by victims of drug-facilitated sexual assault. GHB-glucuronide was firstly identified in urine by the group of Petersen in 2013 and, as per analogy to ethyl glucuronide, it was proposed as a longer biomarker for GHB intoxication.
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Cromatografía Liquida/métodos , Cabello/química , Hidroxibutiratos/análisis , Adulto , Femenino , Toxicología Forense , Glucurónidos/análisis , Glucurónidos/química , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Hidroxibutiratos/química , Lactante , Límite de Detección , Modelos Lineales , Masculino , Espectrometría de Masas , Reproducibilidad de los Resultados , Delitos SexualesRESUMEN
The growing market of herbal remedies worldwide could pose severe problems to consumers' health due to the possible presence of potentially harmful, undeclared synthetic substances or analogues of prescription drugs. The present work shows a simple but effective approach to unequivocally identify synthetic anorectic compounds in allegedly 'natural' herbal extracts, by exploiting liquid chromatography/time of flight (Q-TOF LC/MS) technology coupled to liquid chromatography/triple quadrupole (LC-MS/MS) confirmation and quantitation. The procedure was applied to five tea herbal extracts and pills sold as coadjutant for weigh loss. The method exploited liquid-liquid sample extraction (LLE) and separation in a C18 (2.1mm×150mm, 1.8µm) column. QTOF acquisitions were carried out both in scan mode and all ion MS/MS mode and results were obtained after search against ad hoc prepared library. Sibutramine, 4-hydroxyamphetamine, caffeine and theophylline were preliminary identified samples. Confirmation and quantitation of the preliminary identified compounds were obtained in LC-MS/MS after preparation of appropriated standards. Sibutramine, caffeine and theophylline were finally confirmed and quantitate.
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Fármacos Antiobesidad/química , Depresores del Apetito/análisis , Estimulantes del Sistema Nervioso Central/análisis , Suplementos Dietéticos/análisis , Contaminación de Medicamentos , Cafeína/análisis , Cromatografía Liquida , Ciclobutanos/análisis , Humanos , Extracción Líquido-Líquido , Espectrometría de Masas , Teofilina/análisisRESUMEN
OBJECTIVE: To investigate the feasibility of determining the pattern and prevalence of alcohol consumption in pregnancy by measuring ethanol biomarkers in meconium. DESIGN: Population-based observational study. SETTING: Inner-city maternity unit in Scotland, UK. POPULATION: Random sample of singleton infants delivered after 36 completed weeks' gestation. METHODS: Fatty acid ethyl esters (FAEEs) and ethyl glucuronide (EtG) in meconium were measured by liquid chromatography-mass spectroscopy. Samples were frozen at -20°C before analysis. Results were compared anonymously with demographic data including maternal age, parity, smoking, ethnicity and postcode and with infant gestation, birth weight and head circumference. Written informed consent was obtained from all subjects. RESULTS: 235 samples of meconium were analysed (70% of eligible babies). Only four (1%) of mothers declined to participate. FAAEs were detected in all, including four samples below the limit of quantification (10 ng/g). 98 (42%) samples had FAEE concentrations >600 ng/g. EtG was detectable in 93 (40%) samples; in 35 (15%) EtG concentration was >30 ng/g. No mother reported heavy alcohol consumption in pregnancy. FAAE concentration correlated with EtG (Pearson's coefficient; p<0.001). There was no association between either biomarker and maternal age, parity, smoking, ethnicity or postcode, or infant gestation, birth weight or head circumference. CONCLUSION: Measurement of ethanol biomarkers in meconium is a feasible tool for determining the pattern and prevalence of alcohol consumption in pregnancy. Data suggest that at least 15% of pregnant women in the west of Scotland are consuming significant quantities of alcohol during latter pregnancy.