RESUMO
Introducción: A partir del año 2003, la Agencia Mundial Antidopaje (AMA) comienza a emitir anualmente informes de carácter público donde se informa de todos los análisis realizados y los hallazgos analíticos adversos (HAA) encontrados en los diferentes laboratorios. Objetivos: Identificar los laboratorios europeos y las sustancias prohibidas mayormente reportadas, además de relacionar los HAA en los laboratorios europeos con tres periodos de tiempo diferentes (preolimpiadas, olimpiadas y postolimpiadas). Métodos: Estudio de tipo cohortes, siguiendo las recomendaciones de la declaración STROBE de los informes reportados por la AMA entre los años 2003-2015.Los datos estudiados pertenecen a 16 laboratorios europeos y 11 grupos de sustancias consideradas dopantes. Inclusión: sustancias detectables a través de la orina. Exclusión: tantos los laboratorios que entre 2003-2015 fueran suspendidos temporal o definitivamente por la AMA en Europa, como los de aparición posterior a 2004. Se transformaron las variables de años en preolímpicos, olímpicos y postolímpicos de los Juegos Olímpicos de Atenas (2004) y Londres (2012), por realizarse ambas competiciones en Europa. Resultados: La sustancia más detectada por los laboratorios europeos en los últimos 12 años reportados han sido los anaboli-zantes (52,42%), siendo el laboratorio de Moscú (Rusia) el que mayor detección en dicha sustancia presenta (3 de cada 4 HAA). Se relaciona el aumento de la detección del cannabis en los laboratorios europeos con periodos postolímpicos (p=0,0001). Conclusiones: El laboratorio europeo que proporcionalmente detecta mayor número de HAA es Ghent (Bélgica). Los anabolizantes son la sustancia mayormente detectada en todos los laboratorios. Existe una relación entre la detección de HAA de cannabis en periodos postolímpicos y de anabolizantes en periodos preolímpicos y olímpicos
Introduction: Since 2003, the World Anti-Doping Agency (WADA) begins to provide annual public reports which informs about all the analysis performed and the adverse analytical findings (AAF) determined in the different accredited laboratories. Objectives: To identify the European laboratories and the most used substances for doping purposes, in addition to relate the adverse analytical findings (AAF) in European laboratories over three different periods of time (pre-Olympics, Olympics and post-Olympics). Methods: Cohort study, following the recommendations of the STROBE declaration of the reports collected by the WADA between 2003-2015. The data belong to 16 European laboratories accredited by the WADA distributed in 11 groups of substances considered as doping substances. Inclusion criteria: detectable substances through the urine. Exclusion criteria: laboratories that between 2003-2015 were temporarily or definitively suspended by the WADA or appearance after 2004. The variables of years were transformed into pre-Olympics, Olympics and post-Olympics of the Olympic Games of Athens (2004) and London (2012), because both competitions were carried out in Europe. Results: In the last 12 years reported, the most detected substance by European laboratories has been anabolic substances (52.42%), being the laboratory of Moscow (Russia) which presents the highest detection rate of this substance (3 out of 4 AAF). It is related the increase in the detection of cannabis in the European laboratories with post-Olympics periods (p=0,0001). Conclusions: The laboratory with the highest proportion of AAF reports is Ghent (Belgium). Anabolic steroids are the most commonly detected substance in all the laboratories. There is a relationship between the detection of adverse analytical findings of cannabis in post-Olympics periods and the detection of anabolic steroids in pre-Olympics and Olympics periods
Assuntos
Humanos , Dopagem Esportivo/métodos , Substâncias para Melhoria do Desempenho/administração & dosagem , Anabolizantes/farmacologia , Controle de Medicamentos e Entorpecentes , Entorpecentes/isolamento & purificação , Substâncias para Melhoria do Desempenho/efeitos adversos , Agências Internacionais/normas , Estudos de Coortes , Anabolizantes/análise , Anabolizantes/isolamento & purificação , Estudos Retrospectivos , Estudos Longitudinais , Estudo Observacional , CanabinoidesRESUMO
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief following concerns raised by a reader. The particles shown in Fig. 3F appear to be copies of each other as they share the identical arrangement of the characteristic speckles inside the particles. In addition, the extraordinary similarities observed between the data presented in Fig. 4C and in Fig. 3C in ACS Biomater. Sci. Eng., 2017, 3 (9), pp 21202135, 10.1021/acsbiomaterials.7b00089, Fig. 4A in Colloids and Surfaces B: Biointerfaces, Volume 142, 1 June 2016, Pages 248-258 10.1016/j.colsurfb.2016.02.053 and Fig. 1D in Biosensors and Bioelectronics, Volume 73, 15 November 2015, Pages 234-244, 10.1016/j.bios.2015.06.005 are highly unlikely. The problems with the data presented cast doubt on all the data, and accordingly also the conclusions based on that data, in this publication. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.
Assuntos
Nanopartículas Metálicas/química , Impressão Molecular/métodos , Entorpecentes/isolamento & purificação , Polímeros/química , Prata/química , Tramadol/isolamento & purificação , Adsorção , Carbono/química , Química Verde/métodos , Humanos , Limite de Detecção , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Nanosferas/química , Nanotecnologia/métodos , Entorpecentes/sangue , Entorpecentes/urina , Extração em Fase Sólida/métodos , Tramadol/sangue , Tramadol/urinaRESUMO
In the present work, for the first time, a new portable setup was designed, developed and presented for the extraction of methadone, as a basic drug model from biological fluid samples using a low-voltage electrically stimulated stir membrane liquid-liquid microextraction technique (LV-ESSM-LLME), followed by high-performance liquid chromatography with ultraviolet detection. This new approach combines the advantages of stir membrane liquid-liquid microextraction and electrokinetic migration in the same unit under soft electrochemical conditions in a portable device, allowing for the isolation and preconcentration of the target analyte in a simple and efficient manner under three-phase mode. To investigate the influence of external stirring and the application of electrical potential as the driving force, a comparative study of all variables involved in the extraction process was carried out using the low-voltage electromembrane extraction (LV-EME) and LV-ESSM-LLME methods. Under soft electrokinetic migration conditions, methadone was transported from an acidic sample solution (pH 4.0), through the NPOE immobilized in the pores of the porous polypropylene sheet membrane, and into 25µL of 10mmolL-1 HCl acceptor solution with a stirring rate of 1000rpm and 700rpm after 15min and 20min for LV-ESSM-LLME and LV-EME, respectively. Under the optimized conditions, preconcentration factors in the range of 17-24 and 21.5-29 for LV-EME and LV-ESSM-LLME, respectively, were considered, and satisfactory repeatability (4.5<[RSD]<7.5) was obtained in different matrices. The obtained relative recoveries of the target analyte were in the range of 87-94% and 93-101% for LV-EME and LV-ESSM-LLME, respectively, which indicated the excellent capability of the developed methods to extract methadone from complex matrices.
Assuntos
Líquidos Corporais/metabolismo , Técnicas Eletroquímicas/métodos , Microextração em Fase Líquida/métodos , Metadona/análise , Metadona/isolamento & purificação , Solventes/química , Adulto , Humanos , Masculino , Membranas Artificiais , Entorpecentes/análise , Entorpecentes/isolamento & purificação , Adulto JovemRESUMO
The Scott test, widely used as the field test for cocaine, is performed in three steps. If a sample contains cocaine, blue precipitates appear in step 1, the precipitates are dissolved and the solution turns pink in step 2, and the lower layer turns blue in step 3. However, some pyrrolidine-type cathinones produce cocaine-like results when tested, necessitating modification of the test procedure. Filtration of the second-step mixture weakened the blue color in step 3; however, the blue color did not completely disappear. Adding the Chen-Kao reagent to the test procedure enhanced the differentiation: when the reagent was added to cocaine, the solution was initially turbid, but then became clear over time; its addition to cathinones resulted in turquoise or light sky-blue precipitation. These results indicated that the Chen-Kao test was useful for exclusion of cathinones. A combination of the modified Scott test and the Chen-Kao test was successfully applied to the forensic samples containing cocaine or pyrrolidine-type cathinones. In conclusion, a combination of these tests will be the useful field-test procedure for cocaine.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Cocaína/isolamento & purificação , Entorpecentes/isolamento & purificação , Detecção do Abuso de Substâncias/métodos , Humanos , Indicadores e ReagentesRESUMO
The first step for identification of medicinal plants and their therapeutic effects is to determine their use by local people, traditional medicine books and personal experiences. The aim of this study was to document the medicinal plants used as analgesic, sedative or narcotic agents by local residents of Dehloran, Iran. Interviews conducted with 53 informants (38 male and 15 female) revealed that a total of 32 medicinal plants belonging to 22 families are used in Dehloran as narcotic, sedative and analgesic agents. The most utilized plant families were Asteraceae, Rosaceae and Fabaceae. Approximately 74% of the utilized plants was attributed to herbs, followed by trees (13%) and shrubs (13%). Sixty-six percent of the medicinal plants used in the study area were perennial and the rest were annual or biannual. The most widely used plant parts were flowers (34%) followed by leaves (24%) and fruits (14%). Thirty-nine percent of the medicinal plants were used as sedatives, 39% as analgesics, and 24% as narcotics. Recommended plants in this study can be good candidates for further clinical and laboratory trials on diseases that are associated with pain, suffering, stress and depression. They also can be used to develop new sedative, narcotic and analgesic drugs.
Assuntos
Analgésicos/isolamento & purificação , Hipnóticos e Sedativos/isolamento & purificação , Entorpecentes/isolamento & purificação , Preparações de Plantas/uso terapêutico , Plantas Medicinais , Analgésicos/uso terapêutico , Etnobotânica , Feminino , Humanos , Hipnóticos e Sedativos/uso terapêutico , Irã (Geográfico) , Masculino , Medicina Tradicional , Entorpecentes/uso terapêutico , Fitoterapia/estatística & dados numéricos , Estruturas Vegetais/química , Plantas Medicinais/químicaRESUMO
Monodisperse iron oxide nanocrystals and organic solvents were utilized as coporogens in monolithic poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) capillary columns to afford stationary phases with enhanced electrochromatographic performance of small molecules. While the conventional monoliths using organic solvents only as a porogen exhibited poor resolution (Rs) <1.0 and low efficiency of 40 000-60 000 plates/m, addition of a small amount of nanocrystals to the polymerization mixture provided increased resolution (Rs > 3.0) and high efficiency ranged from 60 000 to 100 000 plates/m at the same linear velocity of 0.856 mm/s. It was considered that the mesopores introduced by the nanocrystals played an important role in the improvement of the monolith performance. This new strategy expanded the application range of the hydrophobic monoliths in the separation of polar alkaloids and narcotics. The successful applications demonstrated that the glycidyl methacrylate based monoliths prepared by using nanocrystal template are a good alternative for enhanced separation efficiency of small molecules.
Assuntos
Eletrocromatografia Capilar/instrumentação , Eletrocromatografia Capilar/métodos , Compostos Férricos/química , Metilmetacrilatos/química , Nanopartículas/química , Modelos Químicos , Entorpecentes/isolamento & purificação , Compostos Orgânicos/isolamento & purificação , PorosidadeRESUMO
The use of thin-film solid-phase microextraction (SPME) as the sampling preparation step before direct analysis in real time (DART) was evaluated for the determination of two prohibited doping substances, cocaine and methadone, in urine samples. Results showed that thin-film SPME improves the detectability of these compounds: signal-to-blank ratios of 5 (cocaine) and 13 (methadone) were obtained in the analysis of 0.5 ng/ml in human urine. Thin-film SPME also provides efficient sample cleanup, avoiding contamination of the ion source by salt residues from the urine samples. Extraction time was established in 10 min, thus providing relatively short analysis time and high throughput when combined with a 96-well shaker and coupled with DART technique.
Assuntos
Cocaína/urina , Inibidores da Captação de Dopamina/urina , Metadona/urina , Entorpecentes/urina , Microextração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Cocaína/isolamento & purificação , Inibidores da Captação de Dopamina/isolamento & purificação , Humanos , Metadona/isolamento & purificação , Entorpecentes/isolamento & purificaçãoRESUMO
A polar polymethacrylate-based monolithic column was introduced and evaluated as a hydrophilic interaction CEC stationary phase. The monolithic stationary phase was prepared by in situ copolymerization of a neutral monomer 2-hydroxyethyl methacrylate and a polar cross-linker N,N'-methylene bisacrylamide in a binary porogenic solvent consisting of dodecyl alcohol and toluene. The hydroxyl and amino groups at the surface of the monolithic stationary phase provided polar sites which were responsible for hydrophilic interactions. The composition and proportion of the polymerization mixture was investigated in detail. The mechanical stability and reproducibility of the obtained monolithic column preformed was satisfied. The effects of pH and organic solvent content on the EOF and the separation of amines, nucleosides, and narcotics on the optimized monolithic column were investigated. A typical hydrophilic interaction CEC was observed on the neutral polar stationary phase. The optimized monolithic column can obtain high-column efficiencies with 62,000-126,000 theoretical plates/m and the RSDs of column-to-column (n = 9), run-to-run (n = 5), and day-to-day (n = 3) reproducibility were less than 6.3%. The calibration curves of these five narcotics exhibited good linearity with R in the range of 0.9959-0.9970 and linear ranges of 1.0-200.0 µg/mL. The detection limits at S/N = 3 were between 0.2 and 1.2 µg/mL. The recoveries of the separation of narcotics on the column were in the range of 84.0-108.6%. The good mechanical stability, reproducibility, and quantitation capacity was suitable for pressure-assisted CEC applications.
Assuntos
Acrilamidas/química , Eletrocromatografia Capilar/instrumentação , Metacrilatos/química , Acetonitrilas/química , Aminas/química , Aminas/isolamento & purificação , Eletrocromatografia Capilar/métodos , Estabilidade de Medicamentos , Eletro-Osmose , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Modelos Químicos , Entorpecentes/química , Entorpecentes/isolamento & purificação , Nucleosídeos/química , Nucleosídeos/isolamento & purificação , Polímeros/síntese química , Polímeros/química , Reprodutibilidade dos TestesRESUMO
An integrated platform for a very sensitive detection of cocaine based on a refractometric biosensor is demonstrated. The system uses a waveguide grating biosensor functionalized with a cocaine multivalent antigen-carrier protein conjugate. The immunoassay scheme consists of the competitive binding of cocaine-specific antibodies to the immobilized conjugates. A 1000-fold enhancement of the sensor's sensitivity is achieved when using gold conjugated monoclonal antibodies instead of free antibodies. Together with the optimization of the assay conditions, the setup is designed for a quick identification of narcotics using automated sampling. The results show that the presence of cocaine in a liquid sample could be identified down to a concentration of 0.7 nM within one minute. This value can be reduced even further when longer binding time is allowed (0.2 nM after 15 min). Application of the system to detection of narcotics at airport security control points is discussed.
Assuntos
Anticorpos Monoclonais/química , Técnicas Biossensoriais/métodos , Cocaína/isolamento & purificação , Entorpecentes/isolamento & purificação , Ouro/química , Humanos , Imunoensaio/métodos , Refratometria/métodosRESUMO
The pharmacological treatment of pain has very ancient origins, when plant-derived products were used, including mandrake extracts and opium, a dried latex obtained from Papaver somniferum. In the XVI and XVII centuries opium came into the preparation of two compounds widely used for pain relief: laudanum and Dover's powder. The analgesic properties of extracts of willow bark were then recognized and later, in the second half of the XIX century, experimental studies on chemically synthesized analgesics were planned, thus promoting the marketing of some derivatives of para-amino-phenol and pyrazole, the predecessors of paracetamol and metamizol. In the XX century, nonsteroidal anti-inflammatory drugs were synthesized, such as phenylbutazone, which was initially considered primarily a pain medication. The introduction on the market of centrally acting analgesics, such as tramadol, sometimes used in the treatment of rheumatic pain, is quite recent.
Assuntos
Analgésicos/história , Antirreumáticos/história , Fitoterapia/história , Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/história , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Europa (Continente) , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História Antiga , História Medieval , Humanos , Entorpecentes/história , Entorpecentes/isolamento & purificação , Entorpecentes/uso terapêutico , Dor/tratamento farmacológico , Extratos Vegetais/história , Extratos Vegetais/uso terapêutico , Doenças Reumáticas/tratamento farmacológicoRESUMO
A new quantitation method for the determination of drugs of abuse (opiates, amphetamine and derivatives, cocaine, methadone and metabolites) in serum by using online extraction coupled to liquid chromatography (LC)-mass spectrometry (MS)/MS has been developed. The online extraction is carried out using two extraction columns simultaneously and one analytical column. One extraction column is loaded, while the other one is eluted by a gradient. The elution gradient also separates the analytes in the analytical column. For the sample preparation, serum is spiked with a mixture of deuterated analogues of the drugs. After protein precipitation with methanol/zinc sulphate, centrifugation, evaporation and reconstitution, the sample is injected into the LC system. The quantitation is based on the analysis of two multiple reaction monitoring transitions per drug. The recovery of the protein precipitation step is over 80% for all analytes. Intra- and interday precision, as relative standard deviation, is lower than 6%, and in the case of accuracy, RE is lower than 15%. Only the most polar analytes showed matrix effects. The limits of quantitation for the analysed compounds vary between 0.5 and 2.8 ng/mL. The developed method was used to quantify basic drugs in samples "from driving under the influence of drugs" cases. The results were compared with those obtained by using solid-phase extraction-GC-MS.
Assuntos
Cromatografia Líquida/métodos , Entorpecentes/análise , Entorpecentes/sangue , Espectrometria de Massas por Ionização por Electrospray/métodos , Detecção do Abuso de Substâncias/métodos , Monitoramento de Medicamentos , Humanos , Entorpecentes/isolamento & purificação , Padrões de ReferênciaRESUMO
Catnip (Nepeta cataria) is known for its pseudo-narcotic effects on cats. Recently, it has been reported as an effective mosquito repellent against several Aedes and Culex species, both topically and spatially. Our laboratory bioassays showed that catnip essential oil (at a dosage of 20 mg) resulted in average repellency rates of 96% against stable flies, Stomoxys calcitrans (L.) and 79% against houseflies, Musca domestica (L.), respectively. This finding suggested that the application of repellent could be used as part of filth fly management. Further evaluations of catnip oil toxicity were conducted to provide a broad-spectrum safety profile of catnip oil use as a potential biting and nuisance insect repellent in urban settings. Acute oral, dermal, inhalation, primary dermal and eye irritation toxicity tests were performed. The acute oral LD(50) of catnip oil was found to be 3160 mg/kg body weight (BW) and 2710 mg/kg BW in female and male rats, respectively. The acute dermal LD50 was > 5000 mg/kg BW. The acute inhalation LD50 was observed to be > 10,000 mg/m3. Primary skin irritation tested on New Zealand white rabbits showed that catnip oil is a moderate irritant. Catnip oil was classified as practically non-irritating to the eye. In comparison with other U.S. Environmental Protection Agency-approved mosquito repellents (DEET, picaridin and p-menthane-3,8-diol), catnip oil can be considered as a relatively safe repellent, which may cause minor skin irritation.
Assuntos
Moscas Domésticas/efeitos dos fármacos , Repelentes de Insetos/isolamento & purificação , Repelentes de Insetos/toxicidade , Nepeta , Óleos Voláteis/farmacologia , Animais , Gatos , DEET/toxicidade , Feminino , Irritantes/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos , Entorpecentes/isolamento & purificação , Entorpecentes/toxicidade , Óleos Voláteis/toxicidade , Coelhos , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/patologiaRESUMO
In Thailand, there are four Mitragyna species; M. speciosa, M. hirsuta, M. diversifolia, and M. rotundifolia. One, M. speciosa, is a narcotic plant and has medicinal importance for its opium-like effect. Since the use of M. speciosa has been forbidden in Thailand, the leaves of M. diversifolia or others are frequently used as substitutes but are not considered as effective. Therefore, accurate authentication of M. speciosa is essential for both medicinal and forensic purposes. The nucleotide sequences of internal transcribed spacers (ITS) and the 5.8S coding region of nuclear ribosomal DNA (rDNA) of the Mitragyna species were analyzed. The whole length of ITS1-5.8S-ITS2 region was 608 bp in M. speciosa, 607 bp in the other species. Nineteen sites of nucleotide substitutions and 3 sites of 1-bp indels were observed, and M. speciosa showed specific sequence differed from the others. Based on the ITS sequences, a distinctive site recognized by a restriction enzyme XmaI in M. speciosa was found and then PCR-restriction fragment length polymorphism (RFLP) analysis was established to differentiate M. speciosa from the others. By the method, a 409-bp PCR fragment of ITS1-5.8S (partial) rDNA region from M. speciosa was cleaved into two fragments of 119 bp and 290 bp while the other species remained undigested. This method provides an effective and accurate identification of M. speciosa.
Assuntos
DNA Espaçador Ribossômico/química , Mitragyna/genética , Entorpecentes/isolamento & purificação , Sequência de Bases , Mitragyna/classificação , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNARESUMO
Four native Papaver species of Iran, i. e. P. glaucum, P. tenuifolium, P. dubium and P. fugax, were collected from their natural habitat and subjected to HPLC analysis for determination of their morphine, codeine and thebaine content. P. dubium and R. glaucum contained all of the three mentioned narcotic alkaloids, while morphine was not found in P. fugax, and P. tenuifolium was free from codeine.
Assuntos
Alcaloides/química , Entorpecentes/química , Papaver/química , Alcaloides/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Codeína/química , Codeína/isolamento & purificação , Irã (Geográfico) , Morfina/química , Morfina/isolamento & purificação , Entorpecentes/isolamento & purificação , Papaver/classificação , Plantas Medicinais/químicaRESUMO
Since 2002, the Istituto Superiore di Sanità, Rome, Italy, in cooperation with Institut Municipal d'Investigaciò Mèdica, Barcelona, Spain, has set up an external proficiency testing program (HAIRVEQ) to evaluate reliability in hair testing for drug abuse by laboratories from the Italian National Health Service. The results obtained in the last 2 rounds (2004-2005) by 26 laboratories and the evolution of the performance in hair testing for drugs of abuse by laboratories that have participated during the whole external proficiency testing program are presented. The 3 hair samples from the last exercise (2005) were also included in the proficiency test organized by the Society of Hair Testing (SoHT) and 17 international laboratories reported results. Samples analyzed in both exercises were real hair samples from drug consumers. In 2004, 2 identical samples were sent containing cocaine and opiates. One sample was a pulverized specimen and the second one was cut in short segments. In 2005, 2 samples, one containing MDMA and another containing cocaine, were included together with one blank sample. In 2004, approximately 42% of HAIRVEQ laboratories reported an erroneous qualitative result. The scatter of quantitative results was high, although no statistical differences, except for codeine, were found between results reported for the hair specimen if pulverized or reduced in short cuts. In 2005, 47 incorrect qualitative results were reported by HAIRVEQ laboratories, whereas only 5 were informed by SoHT laboratories. Concerning quantitative results, the ones from HAIRVEQ laboratories were comparable, although more dispersed, than those reported by SoHT laboratories. The scatter in quantitative results remained quite high and similar to those of the previous years; nonetheless, an improvement in the qualitative performance was observed. Considering the few number of laboratories showing a satisfying performance, guidelines have to be provided focused on method validation and qualitative and quantitative data evaluation.
Assuntos
Técnicas de Laboratório Clínico/normas , Cabelo/química , Avaliação de Programas e Projetos de Saúde , Detecção do Abuso de Substâncias/métodos , 3,4-Metilenodioxianfetamina/análise , 3,4-Metilenodioxianfetamina/isolamento & purificação , Cocaína/análogos & derivados , Cocaína/análise , Cocaína/isolamento & purificação , Codeína/análise , Codeína/isolamento & purificação , Reações Falso-Negativas , Reações Falso-Positivas , Medicina Legal/métodos , Medicina Legal/normas , Humanos , Itália , Laboratórios/normas , Morfina/análise , Morfina/isolamento & purificação , Derivados da Morfina/análise , Derivados da Morfina/isolamento & purificação , N-Metil-3,4-Metilenodioxianfetamina/análise , N-Metil-3,4-Metilenodioxianfetamina/isolamento & purificação , Entorpecentes/análise , Entorpecentes/isolamento & purificação , Peptídeos Opioides/análise , Peptídeos Opioides/isolamento & purificação , Reprodutibilidade dos Testes , Espanha , Distribuições Estatísticas , Detecção do Abuso de Substâncias/normas , Detecção do Abuso de Substâncias/estatística & dados numéricos , Fatores de TempoRESUMO
7-hydroxymitragynine, a constituent of the Thai herbal medicine Mitragyna speciosa, has been found to have a potent opioid antinociceptive effect. In the present study, we investigated the mechanism of antinociception and the inhibitory effect on gastrointestinal transit of 7-hydroxymitragynine, and compared its effects with those of morphine. When administered subcutaneously to mice, 7-hydroxymitragynine produced antinociceptive effects about 5.7 and 4.4 times more potent than those of morphine in the tail-flick (ED50=0.80 mg/kg) and hot-plate (ED50=0.93 mg/kg) tests, respectively. The antinociceptive effect of 7-hydroxymitragynine was significantly blocked by the mu1/mu2-opioid receptor antagonist beta-funaltrexamine hydrochloride (beta-FNA) and the mu1-opioid receptor-selective antagonist naloxonazine in both tests. Thus, 7-hydroxymitragynine acts predominantly on mu-opioid receptors, especially on mu1-opioid receptors. Isolated tissue studies further supported its specificity for the mu-opioid receptors. Further, 7-hydroxymintragynine dose-dependently (ED50=1.19 mg/kg, s.c.) and significantly inhibited gastrointestinal transit in mice, as morphine does. The inhibitory effect was significantly antagonized by beta-FNA pretreatment, but slightly antagonized by naloxonazine. The ED50 value of 7-hydroxymitragynine on gastrointestinal transit was larger than its antinociceptive ED50 value. On the other hand, morphine significantly inhibits gastrointestinal transit at a much smaller dose than its antinociceptive dose. These results suggest that mu-opioid receptor mechanisms mediate the antinociceptive effect and inhibition of gastrointestinal transit. This compound induced more potent antinociceptive effects and was less constipating than morphine.
Assuntos
Analgésicos/farmacologia , Trânsito Gastrointestinal/efeitos dos fármacos , Mitragyna/química , Receptores Opioides mu/fisiologia , Alcaloides de Triptamina e Secologanina/farmacologia , Analgésicos/química , Analgésicos/isolamento & purificação , Analgésicos Opioides/farmacologia , Animais , Relação Dose-Resposta a Droga , Trânsito Gastrointestinal/fisiologia , Cobaias , Medicina Herbária , Íleo/efeitos dos fármacos , Íleo/fisiologia , Masculino , Camundongos , Estrutura Molecular , Morfina/farmacologia , Contração Muscular/efeitos dos fármacos , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Entorpecentes/química , Entorpecentes/isolamento & purificação , Entorpecentes/farmacologia , Dor/fisiopatologia , Dor/prevenção & controle , Medição da Dor/métodos , Receptores Opioides mu/antagonistas & inibidores , Alcaloides de Triptamina e Secologanina/química , Alcaloides de Triptamina e Secologanina/isolamento & purificação , Tailândia , Ducto Deferente/efeitos dos fármacos , Ducto Deferente/fisiologiaRESUMO
The new definition of the term sudden infant death syndrome (SIDS) and the criteria introduced in San Diego for the subclassification of cases have been used to re-classify the first 100 consecutive cases of sudden and unexpected infant deaths that were registered with the German SIDS study (GeSID). Although there are 30 different variables that have to be considered in the general and stratified sections of the San Diego definition, it is practical, in particular, as an international standard to perform scientific studies. The comparison of the San Diego definition and the classification used for GeSID shows similarities in the methods but differences in the criteria used. Nevertheless, the numbers of cases classified as SIDS and borderline SIDS are similar (San Diego n=69, GeSID n=74). The SIDS IA criteria of the San Diego definition were not fulfilled by any case because metabolic screening and vitreous chemistry were not included in the GeSID investigation scheme. An important advantage of the San Diego definition is the introduction of the category of unclassified sudden infant death, which includes cases for which no autopsy was performed. This demonstrates that such cases cannot be classified as SIDS. In conclusion, we recommend the universal acceptance and use of the San Diego SIDS definition.
Assuntos
Medicina Legal , Morte Súbita do Lactente/classificação , Morte Súbita do Lactente/diagnóstico , Distribuição por Idade , Roupas de Cama, Mesa e Banho , California , Maus-Tratos Infantis/diagnóstico , Desenvolvimento Infantil , Alemanha , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Inflamação/patologia , Metadona/isolamento & purificação , Entorpecentes/isolamento & purificação , Irmãos , Sono , Timo/patologiaRESUMO
High-performance liquid chromatography (HPLC) separation of drugs at elevated pressure with 1.7 microm hybrid C18 stationary phase columns was investigated. This technique, which uses instrumentation engineered to handle the narrow peaks and high back pressures generated by 1.7 microm particle columns, provided significantly better resolution and/or faster analysis than conventional HPLC and capillary electrophoresis (CE). The use of 2mm internal diameter (i.d.) columns of 3-10 cm length has been evaluated for the separation of basic and neutral drugs, drug profiling, and general screening (including acidic drugs). For these applications, compared to conventional HPLC and CE, it provided up to 12x and 3x faster analyses, respectively. Precision was excellent for both isocratic and gradient analyses. For retention time and peak area, RSDs of < or =0.1% were obtainable. Fifteen anabolic steroids and esters were well separated in a 2.5 min gradient. For drug profiling, compared to HPLC and CE, approximately twice as many peaks were resolved. HPLC at elevated pressure is also well suited as a general screening technique. Twenty-four solutes of varying drug classes including narcotic analgesics, stimulants, depressants, hallucinogens, and anabolic steroids were fully separated in a 13.5 min gradient.
Assuntos
Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , Preparações Farmacêuticas/análise , Alcanos , Anabolizantes/isolamento & purificação , Depressores do Sistema Nervoso Central/isolamento & purificação , Estimulantes do Sistema Nervoso Central/isolamento & purificação , Ciências Forenses , Alucinógenos/isolamento & purificação , Drogas Ilícitas/análise , Entorpecentes/isolamento & purificação , Preparações Farmacêuticas/isolamento & purificação , PressãoRESUMO
There are three types of opiate alkaloids. First, the poppy alkaloids: morphine, codeine, thebaine, noscapine and papaverine; then, the semi-synthetic and synthetic derivatives used in therapy as antitussives and analgesics, such as pholcodine, ethylmorphine and dextromethorphan; at last narcotic compounds, diacetylmorphine (heroin) and opiates employed as substitutes in treatment of addiction: buprenorphine and methadone. For classical thin-layer chromatography (TLC) of opium alkaloids, it is necessary to use complex eluents with strong alkaline substances to obtain a clean separation between morphinan and isoquinoline compounds. This study purposes the planar chromatographic analysis of these substances by the automated multiple development (AMD) compared with results obtained by classical TLC method. The aim of this work was to achieve the best separation of these opiate alkaloids and derivatives by this modern technique of planar chromatography. The AMD system provided a clean separation for each of three opiates groups studied and the best results have been obtained with universal gradient: methanol 100, methanol-dichloromethane 50/50, dichloromethane 100, dichloromethane 100, hexane 100 for opium alkaloids and with gradient A: 5% of 28% ammonia in methanol 100, acetone 100, acetone 100, ethyl acetate-dichloromethane 50/50, dichloromethane 100 for antitussives and substitutes. Two reagents were used for the detection of alkaloids by spraying: Dragendorff and iodoplatinate reagents. The detection limits with these two reagents were 1 microg for ethylmorphine, thebaine, papaverine, codeine, and 2 microg for morphine and noscapine and other alkaloids.
Assuntos
Cromatografia em Camada Fina/métodos , Entorpecentes/isolamento & purificação , Ópio/isolamento & purificação , Antitussígenos/isolamento & purificação , Morfinanos/isolamento & purificação , Morfolinas/isolamento & purificação , Reprodutibilidade dos TestesRESUMO
A capillary electrophoresis method was developed to detect interactions between methadone and anti-retroviral compounds. Eight subjects, who underwent methadone maintenance treatment in the Province of Alicante (Spain), consented to participate in the present study. Of those, one subject was followed up for 123 days to detect drug-drug interactions. The enantiomers of methadone and those of its main metabolite were conveniently resolved within 4 min using a chiral electrophoresis buffer mixture which consisted of phosphate buffer, pH 5, plus 0.2% highly sulphated-(beta)-cyclodextrin. The effective mobility of the analytes was in the 0.061-0.140 cm(2)/(kV s) range at pH 5. The R-methadone plasma concentration range for seven patients was 91-318 ng/mL, it decreased from 186 to 46 ng/mL in a patient followed-up on commencement of the anti-retroviral therapy, returning to the previous higher levels after progressive dose increases. We conclude that monitoring R-methadone plasma levels can be a useful tool for the dose adjustment of methadone.