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1.
Toxicol Appl Pharmacol ; 426: 115649, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34273407

RESUMEN

The use of the anthelmintic levamisole as a cocaine adulterant has been increasing worldwide. Complications caused by this association include systemic vasculitis, agranulocytosis, neutropenia, tissue necrosis, pulmonary hemorrhage, and renal injury. Data about toxicity of levamisole are scarce, therefore the aim of this study was to evaluate the acute and subchronic toxic effects of levamisole in rats. Male Wistar rats received saline or levamisole by intraperitoneal route at the doses of 12, 24 and 36 mg/kg in the acute toxicity test; and at 3, 6 and 12 mg/kg in the subchronic toxicity test. Toxicity was evaluated using behavioral, cognitive, renal, hematological, biochemical and histopathological parameters. Acute administration of levamisole caused behavioral and histopathological alterations. Subchronic administration caused behavioral, cognitive and hematological alterations (p < 0.0001 and p < 0.05, respectively), impairment of liver and kidney functions (p < 0.05), and changes of antioxidant defenses (p ≤ 0.0001). Both administrations produced toxic effects of clinical relevance, which make levamisole a dangerous cutting agent. Furthermore, the knowledge of these effects can contribute to the correct diagnosis and treatment of cocaine dependents with unusual systemic alterations.


Asunto(s)
Antinematodos/toxicidad , Levamisol/toxicidad , Síndromes de Neurotoxicidad/etiología , Animales , Conducta Animal/efectos de los fármacos , Cocaína , Recuento de Leucocitos , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Síndromes de Neurotoxicidad/inmunología , Síndromes de Neurotoxicidad/metabolismo , Síndromes de Neurotoxicidad/patología , Tamaño de los Órganos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Pruebas de Toxicidad Aguda
2.
J Anal Toxicol ; 48(5): 314-331, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38334744

RESUMEN

Urine toxicological analysis is a relevant tool in both clinical and forensic scenarios, enabling the diagnosis of acute poisonings, elucidation of deaths, verification of substance use in the workplace and identification of drug-facilitated crimes. For these analyses, the dilute-and-shoot technique associated with liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) is a promising alternative since it has demonstrated satisfactory results and broad applicability. This study developed and validated a comprehensive LC-MS-MS screening method to analyze 95 illicit drugs and medicines in urine samples and application to clinical and forensic Brazilian cases. The dilute-and-shoot protocol was defined through multivariate optimization studies and was set using 100 µL of sample and 300 µL of solvent. The total chromatographic run time was 7.5 min. The method was validated following the recommendations of the ANSI/ASB Standard 036 Guideline. The lower limits of quantification varied from 20 to 100 ng/mL. Within-run and between-run precision coefficient of variations% were <20%, and bias was within ± 20%. Only 4 of the 95 analytes presented significant ionization suppression or enhancement (>25%). As proof of applicability, 839 urine samples from in vivo and postmortem cases were analyzed. In total, 90.9% of the analyzed samples were positive for at least one substance, and 78 of the 95 analytes were detected. The most prevalent substances were lidocaine (40.2%), acetaminophen (38.0%) and benzoylecgonine (31.5%). The developed method proved to be an efficient and simplified alternative for analyzing 95 therapeutic and illicit drugs in urine samples. Additionally, the results obtained from sample analysis are essential for understanding the profile of Brazilian substance use, serving as a valuable database for the promotion of health and safety public policies.


Asunto(s)
Toxicología Forense , Drogas Ilícitas , Detección de Abuso de Sustancias , Espectrometría de Masas en Tándem , Humanos , Drogas Ilícitas/orina , Brasil , Detección de Abuso de Sustancias/métodos , Cromatografía Liquida , Toxicología Forense/métodos , Reproducibilidad de los Resultados , Límite de Detección , Cromatografía Líquida con Espectrometría de Masas
3.
Bioanalysis ; 15(16): 1021-1032, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37431824

RESUMEN

Background: The increasing prevalence of poisoning cases related to antidepressants and antipsychotics has raised concerns. Methods: To address this issue, a new adaptation of the dried plasma spot technique was developed using a 24-well plate and fast gas chromatography-mass spectrometry. The method involves the optimization of extraction variables and sample preparation, and was successfully validated. Results: The limits of quantitation ranged from 20 to 60 ng/ml, and accuracy ranged from 87.8% to 112.2%. The technique was applied to 102 human plasma samples from suspected poisoning cases, with positivity of 90.2%. Conclusion: This method provides a cheap, easy to implement and fast approach, making it ideal for toxicological emergency laboratories and promoting valuable support for healthcare professionals managing poisoning cases involving antidepressants and antipsychotics.


Asunto(s)
Antipsicóticos , Humanos , Cromatografía de Gases y Espectrometría de Masas/métodos , Espectrometría de Masas en Tándem/métodos , Antidepresivos , Plasma , Pruebas con Sangre Seca/métodos , Reproducibilidad de los Resultados
4.
J Pharm Biomed Anal ; 222: 115082, 2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36183577

RESUMEN

The diagnostic methods in an emergency scenario must be simple, fast, and efficient to provide an effectiveness and efficient treatment, thus reducing the consequences of exposure. Considering the sample analysis, the protein precipitation combined with LC-MS/MS has been shown to be a good strategy for the simultaneous determination of compounds of toxicological interest, such as medicines and drugs of abuse. In this study, a rapid and simple multi-analyte method was developed and validated for the quantification of 57 pharmaceuticals and illicit drugs in plasma samples. Sample pre-treatment consists of protein precipitation of 50 µL of the sample with 240 µL of organic solvent mixture (MeOH:ACN, 3:1, v/v), centrifugation, and injection into the LC-MS/MS, with a chromatographic run time of 7 min. The method was validated considering lower limit of quantification (LLOQ), interferences, linearity, precision, accuracy, dilution integrity, carryover, and matrix effect. The LLOQs ranged from 5 to 20 ng/mL and all analytes were linear (r2>0.99) in the tested concentration ranges. The method proved to be precise and accurate, presenting QC concentrations for all analytes within acceptable limits by the guideline used (CV % ≤20 % and bias ± 20 %). The developed method was successfully applied in 470 plasma samples of real cases of poisoning. A total of 80 % of the samples were positive for at least one substance, with acetaminophen (32.1 %), diazepam (25.1 %), and lidocaine (18.9 %) being the most detected. The most prevalent exposure circumstance among the cases was suicide attempt. The most frequent age groups were young adults between 20 and 29 years old and children under 5 years old. The methodology developed proved to be efficient in the simultaneous determination of 57 substances of toxicological interest, contributing to a correct diagnosis and, consequently, to the most appropriate management and treatment of the intoxicated patient. Furthermore, it is possible to observe the most commonly involved toxic agents in the Rio Grande do Sul, southern Brazil, helping to trace a profile of the poisoning patient, important in toxicovigilance actions.


Asunto(s)
Drogas Ilícitas , Humanos , Niño , Preescolar , Adulto Joven , Adulto , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Plasma , Brasil , Reproducibilidad de los Resultados , Límite de Detección
5.
Artículo en Inglés | MEDLINE | ID: mdl-35649678

RESUMEN

Pollution of aquatic ecosystems is associated with the discharge of mainly industrial and urban effluents, which may cause damage to public health. This study aims to evaluate the cytotoxic, genotoxic, and mutagenic potential of surface water samples under the influence of different anthropogenic effluents in a human-derived liver cell line (HepG2). Samples were collected in Esteio and Sapucaia streams (Rio Grande do Sul; Brazil), which flow into the Sinos River, a source of water supply for more than one million people. Physicochemical and microbiological analyses were performed as well as an analysis of inorganic elements using the PIXE technique (Particle-Induced X-Ray Emission). The presence of pharmaceutical compounds and caffeine was evaluated by gas chromatography coupled to mass spectrometry. The cytotoxicity, genotoxicity, and mutagenicity of the samples were evaluated in HepG2 cells by cell viability assays, alkaline Comet Assay and Cytokinesis-block micronucleus (CBMN) assay. We verified alterations in the physicochemical and microbiological parameters and detected caffeine, diethyltoluamide, and different inorganic elements that corresponded to elements from domestic and industrial effluents and agricultural runoff. Although the samples in the concentration used were not cytotoxic, water samples from all sites induced DNA damage. However, it is difficult to attribute these damages to a specific substance since the factors are a complex mixture of different compounds. Despite this, it is observed that both urban and industrial contributions had a similar effect in the cells evaluated. Such results demonstrate the need to perform biomonitoring of surface waters under anthropogenic influence, especially those that flow into rivers that are a source of public supply water. We also highlight the need for research into emerging pollutants in these aquatic environments.


Asunto(s)
Ríos , Contaminantes Químicos del Agua , Efectos Antropogénicos , Brasil , Cafeína , Daño del ADN , Ecosistema , Monitoreo del Ambiente/métodos , Humanos , Mutágenos/análisis , Mutágenos/toxicidad , Ríos/química , Agua , Contaminantes Químicos del Agua/toxicidad
6.
Arch Toxicol ; 83(1): 95-9, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18651134

RESUMEN

Formulations containing Ephedra sinica Stapf. (Ephedraceae) and Citrus aurantium L. (Rutaceae) are consumed worldwide for body weight control. Considering the related adverse effects and the risk potential, the aim of this study is to evaluate the effects of the thermogenic compounds ephedrine, p-sinephrine, E. sinica and C. aurantium in the female reproductive system through the uterotrophic assay in immature female rats. The animals (n = 6-7) received E. sinica 85.5 and 855.0 mg/kg/day, C. aurantium 25.0 and 50.0 mg/kg/day, ephedrine 5.0 mg/kg/day and p-synephrine 50.0 mg/kg/day for three consecutive days by oral gavage. For detection of antiestrogenicity, tamoxifen 20.0 mg/kg/day, E. sinica 855.0 mg/kg/day, C. aurantium 50.0 mg/kg/day, ephedrine 5.0 mg/kg/day and p-synephrine 50.0 mg/kg/day were administered to estrogen-treated females. Macroscopical alterations were evaluated in liver, kidneys, adrenals and uterus. All analyzed substances showed an antiestrogenic potential, but only ephedrine at 0.5 mg/kg/day presented a significative antiestrogenic effect (P < 0.01). Adrenals relative mass were reduced (P < 0.01) in all tested compounds when compared to the control, which seems to be related to the alfa-1-adrenoceptor agonist activity, which promote a vasoconstriction and reduction of the liquid in the organ. The endocrine system is highly complex and there are a number of ways in which a chemical may interfere with it, other in vivo and in vitro assays are being necessary to support this mechanism of action.


Asunto(s)
Citrus/química , Ephedra sinica/química , Efedrina/toxicidad , Sinefrina/toxicidad , Administración Oral , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/metabolismo , Adrenérgicos/aislamiento & purificación , Adrenérgicos/toxicidad , Agonistas alfa-Adrenérgicos/aislamiento & purificación , Agonistas alfa-Adrenérgicos/toxicidad , Animales , Relación Dosis-Respuesta a Droga , Efedrina/aislamiento & purificación , Moduladores de los Receptores de Estrógeno/aislamiento & purificación , Moduladores de los Receptores de Estrógeno/toxicidad , Femenino , Extractos Vegetales/administración & dosificación , Extractos Vegetales/toxicidad , Ratas , Ratas Wistar , Sinefrina/aislamiento & purificación , Útero/efectos de los fármacos , Útero/metabolismo
8.
J. bras. patol. med. lab ; J. bras. patol. med. lab;46(2): 143-148, abr. 2010. graf, tab
Artículo en Portugués | LILACS | ID: lil-552260

RESUMEN

INTRODUÇÃO E OBJETIVO: Paracetamol ou acetaminofeno é atualmente um dos analgésicos-antipiréticos mais utilizados, principalmente em crianças. Porém o fácil acesso ao medicamento e o desconhecimento da população sobre seus efeitos nocivos têm aumentado muito o número de intoxicações por esse medicamento. A análise da concentração sérica de paracetamol confirma o diagnóstico. O resultado não só tem valor de certeza diagnóstica como também avalia o risco de hepatotoxicidade, indicando uso ou não do antídoto específico n-acetilcisteína. O objetivo deste trabalho foi propor um método analítico para quantificação sérica do paracetamol por espectrofotometria visível em 430 nm. MATERIAIS E MÉTODOS: Após desproteinização da amostra, acetaminofeno (n-acetil-p-aminofenol) reage com nitrito de sódio, formando 2,4-nitro-4-acetaminofenol, que assume coloração amarela em meio alcalino. As figuras de mérito linearidade, precisão, exatidão, robustez, recuperação, limites de detecção e qualificação foram avaliadas segundo critérios preconizados pelo International Conference on Harmonisation (ICH) e pela Agência Nacional de Vigilância Sanitária (ANVISA). O estudo de estabilidade foi realizado após ciclos de congelamento/descongelamento, curta duração, longa duração sob refrigeração e em freezer. RESULTADOS: O método se mostrou linear de 20 a 300 mg/l. Os limites de detecção e quantificação foram de respectivamente 3,6 mg/l e 20 mg/l. CONCLUSÃO: O método se mostrou preciso, exato e robusto e apresentou boa recuperação. As amostras-controle foram estáveis nas condições testadas. O método desenvolvido demonstrou possuir todos os parâmetros necessários para ser aplicado na quantificação de paracetamol em amostras de plasma ou soro humano para análise de emergência. Além disso, é uma técnica simples, de rápida execução e baixo custo.


INTRODUCTION AND OBJECTIVE: Acetaminophen or paracetamol is currently one of the most used analgesic-antipyretic agents, mainly with children. However, both the easy access to this medicine and the population's unawareness of its toxic effects have contributed to a rise in the number of intoxications caused by this drug. Assessment of serum acetaminophen confirms the diagnosis. Not only does the result have diagnostic reliability but it also evaluates the risk of hepatotoxicity, indicating or not the administration of the specific antidote n-acetylcysteine. The aim of this study is to present an analytical method to the assessment of serum acetaminophen by spectrophotometric detection at 430 nm. MATERIALS AND METHODS: After sample deproteinization, acetaminophen (n-acetyl-p-aminophenol) reacts with sodium nitrite forming 2.4-nitro-4-acetaminophenol, which becomes yellowish in alkaline medium. For method validation, linearity, precision, accuracy, robustness, recovery and detection limits were evaluated according to ICH and ANVISA criteria. The stability study was carried out after freezing/defreezing cycles, short-time duration, long-time duration under refrigeration and long-time duration under freezing. RESULTS: The method showed to be linear from 20 to 300 mg/l. The detection and quantification limits were 3.6 mg/l and 20 mg/l, respectively. CONCLUSION: The method was precise, accurate and robust and showed good recovery. The control-samples were stable in all tested conditions. The method developed presented all the necessary parameters to be applied in acetaminophen quantification in plasma samples or human serum for emergency analyzes. Furthermore, it is a simple, time and cost-effective technique.


Asunto(s)
Acetaminofén/análisis , Acetaminofén/sangre , Acetaminofén , Acetaminofén/envenenamiento
9.
Rev. bras. farmacogn ; 18(3): 394-401, jul.-set. 2008. ilus
Artículo en Portugués | LILACS | ID: lil-496115

RESUMEN

Amostras de Ephedra tweediana Fisch & C.A. Meyer, coletadas de populações nativas da Reserva Biológica do Lami José Lutzenberger (Porto Alegre, RS, Brasil), e amostras de Ephedra triandra Tul., obtidas de plantas cultivadas em Porto Alegre/RS, foram extraídas com acetona, derivatizadas com ciclohexanona e analisadas por CG/EM. Para verificação da eficiência da metodologia, além das amostras de Ephedra tweediana e E. triandra, foram analisadas cinco amostras comerciais de Ephedra, de procedências distintas, cedidas por farmácias de manipulação locais. Os resultados encontrados indicam a ausência de efedrinas em Ephedra tweediana e E. triandra e presença de efedrina e/ou pseudoefedrina nas amostras comerciais.


Samples of Ephedra tweediana, collected from native populations occurring in the Reserva Biológica do Lami José Lutzenberger (Porto Alegre, RS, Brazil), and from cultivated plants of Ephedra triandra were submitted to extraction with acetone, derivatized with cyclohexanone and analyzed by GC/MS. In order to verify the efficiency of the methodology, besides Ephedra tweediana and E. triandra, samples of five commercial Ephedra extracts were analyzed, from distinct origins, get up from local drugstores. The results showed the absence of ephedrines in Ephedra tweediana and E. triandra, and the presence of ephedrine and/or pseudoephedrine in commercial samples.

10.
Rev. bras. saúde ocup ; 30(111): 51-56, jan.-jun. 2005. tab
Artículo en Portugués | LILACS | ID: lil-659074

RESUMEN

Este estudo tem como objetivo investigar a relação entre a perda auditiva e a exposição ocupacional ao ruído e ao tolueno. A população em estudo foi composta por 73 trabalhadores de curtume. Para conhecer a história clínica e ocupacional dos trabalhadores, aplicou-se um questionário. Para avaliação da exposição ocupacional, realizaram-se avaliações ambiental e biológica do tolueno e avaliações audiológica e dos níveis de ruído. Os valores obtidos na avaliação ambiental e biológica estavam abaixo dos limites estabelecidos pelas NR 7 e 15. Os níveis de ruído em diversos setores da indústria foram superiores ao máximo permitido pela NR 15, chegando a 97.8 dB(A). As perdas auditivas encontradas no grupo ruído (GR) e no grupo ruído e agente químico (GRAQ) foram significativas quando comparadas ao grupo controle através da análise estatística SPSS®, T-Test p<0,01. Este estudo demonstrou fatores de impacto na saúde e na qualidade de vida dos trabalhadores. Portanto, fazem-se necessárias a revisão dos programas e a implementação de medidas que reduzam os riscos de forma a prevenir e evitar danos à saúde do trabalhador.


This study aims at investigating the relationship between the hearing loss and the occupational exposition to noise and toluene. Seventy-three tannery workers were the subject of this study. A questionnaire was used to obtain information on the workers' clinical and occupational history. To evaluate the occupational exposition, an environmental and biological survey on toluene was held, together with noise and audiologycal evaluations. The results of the environmental and biological evaluations were below the levels established by NR 7 and 15. The noise levels in several sections of the industry were above the maximum allowed by NR 15, reaching 97.8dB(A). The hearing losses found in the noise group (GR) and noise and chemical agents (GRAQ) groups were significant when compared, through the statistic analysis SPSS®, T-Test p<0,01, to the control group. This study demonstrated impact factors in workers' health and life quality. Due to this, the programs must be revised and measures to reduce the risks must be implemented in order to prevent hazards to workers' health.

11.
Acta méd. (Porto Alegre) ; 27: 473-480, 2006.
Artículo en Portugués | LILACS | ID: lil-445176

RESUMEN

Com base no reconhecimento da importância da monitorização terapêutica, as autoras fazem uma revisão dos aspectos relacionados à determinação dos níveis séricos de fármacos em situações de intoxicação.


Asunto(s)
Humanos , Evaluación de Medicamentos , Monitoreo de Drogas
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