RESUMO
Omarigliptin (OMG) is an antidiabetic drug indicated for the treatment of type 2 diabetes mellitus. Forced degradation studies are practical experiments to evaluate the stability of drugs and to establish degradation profiles. Herein, we present the investigation of the degradation products (DPs) of OMG formed under various stress conditions. OMG was subjected to hydrolytic (alkaline and acidic), oxidative, thermal, and photolytic forced degradation. A stability-indicating ultra-fast liquid chromatography method was applied to separate and quantify OMG and its DPs. Five DPs were adequately separated and detected in less than 6 min, while other published methods detected four DPs. MS was applied to identify and obtain information on the structural elucidation of the DPs. Three m/z DPs confirmed previously published research, and two novel DPs were described in this paper. The toxicity of OMG and its DPs were investigated for the first time using in vitro cytotoxicity assays, and the sample under oxidative conditions presented significant cytotoxicity. Based on the results from forced degradation studies, OMG was found to be labile to hydrolysis, oxidation, photolytic, and thermal stress conditions. The results of this study contribute to the quality control and stability profile of OMG.
Assuntos
Estabilidade de Medicamentos , Compostos Heterocíclicos com 2 Anéis , Piranos , Cromatografia Líquida de Alta Pressão/métodos , Piranos/química , Piranos/análise , Piranos/toxicidade , Compostos Heterocíclicos com 2 Anéis/química , Compostos Heterocíclicos com 2 Anéis/análise , Compostos Heterocíclicos com 2 Anéis/toxicidade , Espectrometria de Massas/métodos , Humanos , Sobrevivência Celular/efeitos dos fármacos , Reprodutibilidade dos Testes , Hipoglicemiantes/química , Hipoglicemiantes/análise , Oxirredução , Modelos LinearesRESUMO
Pterostilbene (PTS) is a drug candidate with low water solubility and poor bioavailability. On the other hand, drug:cyclodextrins complexes frequently provide bulk powders with low drug concentrations, which is crucial for obtention solid or semi-solid pharmaceutical dosage forms. In order to determine the optimal conditions for enhancing the solubility of PTS:BCD (ß-cyclodextrin) complex, a Box-Behnken design was performed. Although the optimal conditions have been applied, low complexation efficiency (0.127) and the bulk powder remained. A PTS:BCD:HPMC (HPMC, hydroxypropyl methylcellulose) ternary system was developed to overcome this limitation, comparing two media, water and a mixture of ethanol-water. When ethanol was used as a co-solvent, the PTS:BCD:HPMC ternary system (freeze-dried) contained 116.65 ± 1.40 mg/g of PTS. This value was 3.4-fold higher than the PTS content observed when the same ternary system was obtained in aqueous media (34.8 mg/g) and 2.8-fold higher than the PTS content observed for PTS:BCD complex (freeze-dried) obtained using ethanol as a co-solvent. Dissolution tests revealed that after 120 min, in a buffer with a pH value of 1.2, only 43% of PTS dissolved. In contrast, 80% and 90% of PTS were dissolved from the PTS:BCD complex and PTS:BCD:HPMC ternary system, respectively. Moreover, the dissolution was fast in a buffer with a pH value of 6.8. PTS:BCD complex reached the maximum PTS dissolution at 75 min and PTS:BCD:HPMC at 45 min. In summary, the results of this study demonstrated, for the first time, that low-bulk powders with a high content of PTS can be obtained from PTS:BCD:HPMC ternary systems using ethanol as a co-solvent. This new finding offers a valuable alternative for producing solid or semi-solid formulations containing highly soluble PTS.
Assuntos
Química Farmacêutica , Água , Solubilidade , Pós , Química Farmacêutica/métodos , Derivados da Hipromelose , Água/química , SolventesRESUMO
Vancomycin is used as an antimicrobial agent for the treatment of severe gram-positive infections. The importance of therapeutic monitoring of antimicrobials has led to the development of more specific sample preparation techniques capable of identifying with accuracy the concentration of this substance in the organism. An aliquot of 10 µl of plasma was transferred to Whatman 903 paper and dried at room temperature. The extraction method was performed by cutting and transferring the paper to a microtube and adding sodium phosphate buffer and internal standard. The mixture was shaken and centrifuged, and a 5-µl aliquot was injected into the analytical system. The optimization of the main parameters that can influence the extraction efficiency was performed using multivariate approaches to obtain the best conditions. The method developed was validated, providing coefficients of determination higher than 0.994 and a lower limit of quantification of 1 mg/L. Within- and between-run precision ranged from 11.4 to 17.30% and from 6.65 to 13.51%, respectively. This method was successfully applied to 75 samples of patients undergoing vancomycin therapy. The method was rapid, simple, and environmentally friendly with satisfactory analytical performance and was advantageous over the laborious and time-consuming methodologies used in therapeutic drug monitoring routine analyses.
Assuntos
Espectrometria de Massas em Tandem , Vancomicina , Humanos , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Plasma , Monitoramento de Medicamentos/métodos , Teste em Amostras de Sangue Seco/métodos , Imunoensaio/métodos , Reprodutibilidade dos TestesRESUMO
Electroosmotic flow (EOF) was determined in tridimensional (3D)-printed microchannels with dimensions smaller than 100 µm. Fused deposition modeling 3D printing using thermoplastic filaments of PETG (polyethylene terephthalate glycol), PLA (polylactic acid), and ABS (acrylonitrile butadiene styrene) were used to fabricate the microchannels. The current monitoring method and sodium phosphate solutions at different pH values (3-10) were used for the EOF mobility (µEOF ) measurements, which ranged from 2.00 × 10-4 to 12.52 × 10-4 cm2 V-1 s-1 . The highest and the smallest µEOF were obtained for the PLA and PETG microchannels, respectively. Adding the cationic surfactant cetyltrimethylammonium bromide to the sodium phosphate solution caused EOF direction reversion in all the studied microchannels. The obtained results can be interesting for developing 3D-printed microfluidic devices, in which EOF is relevant.
Assuntos
Eletro-Osmose , Fosfatos , Eletro-Osmose/métodos , Impressão TridimensionalRESUMO
BACKGROUND: The analysis of plant material from Cannabis sativa L. has long been targeted on its main psychologically active metabolite, Δ9-tetrahydrocannabinol (THC). In addition to the diverse plant composition and medicinal interest in several cannabinoids, these compounds may also be related to the different characteristics of samples sold illegally. Currently, it is indisputable that other cannabinoids should also be considered in cannabis assays. Mass spectrometry has been used to identify and characterize substances in the most different scenarios, and knowing the analyte fragmentation profile is essential for characterizing samples of diverse origin. OBJECTIVE: In this work, flow injection analysis-tandem mass spectrometry with electrospray ionization (FIA-ESI-MS/MS) in positive and negative modes was used to evaluate the fragmentation profiles of eight cannabinoids commonly found in cannabis samples: THC, tetrahydrocannabinolic acid, Δ8-tetrahydrocannabinol, cannabidiol, cannabidiolic acid, cannabigerol, cannabigerolic acid and cannabinol. METHODS: By exploring the fragmentation data from mass spectrometry, the samples were classified using a chemometric model of partial least squares discriminant analysis (PLS-DA). RESULTS: When ESI in negative mode is used with adequate collision energies, it is possible to identify differences in the fragmentation of isomers. Based on that, chemometric tools were employed to classify different samples. The PLS-DA applied to FIA-ESI-MS/MS data yielded satisfactory classification. CONCLUSION: Thus, the results presented can be applied as a preliminary tool in the analysis of unknown samples, guiding more accurate investigations in terms of chemical composition. HIGHLIGHTS: This study of the cannabinoid fragmentation pattern by flow injection MS showed that cannabinoids can be distinguished by their fragmentation spectra after negative electrospray ionization. Multivariate data analysis (PLS-DA) allowed classification of different cannabis samples.
Assuntos
Canabinoides , Cannabis , Alucinógenos , Canabinoides/análise , Cannabis/química , Dronabinol/análise , Análise de Injeção de Fluxo , Espectrometria de Massas em Tandem/métodosRESUMO
INTRODUCTION: The presence of anabolic-androgenic steroids (AAS) in illegal commercial products has been pointed as a global threat for public health. Due the correlation with adverse toxicological effects, there is a growing interest in the implementation of straightforward methods for the determination of AAS in seized products. This work exploited the development of a mass spectrometry approach to characterize the illegal oil formulations containing AAS. METHODS: The optimization of sample preparation was performed through a simplex-centroid design and the best condition was described as follow: an aliquot of 5 µL of sample were added with 995 µL of acetonitrile and water (75:25, v/v). The solution was vortexed and centrifuged. After that, 10 µL of supernatant were added with 35 µL of acetonitrile and water and internal standard (testosterone-d3, 1.25 ng). An aliquot of 5 µL was injected into the analytical system. RESULTS: The method developed was validated and successfully applied in 115 seized samples. Testosterone and its esters had the highest incidence, found in more than 50% of the samples. Besides that, drugs such as boldenone, methandienone, and trenbolone have also been found, where the low quality of the samples was evidenced by the wide variation in the concentration of the drugs, always quantified in sub-doses. Finally, at least one AAS was detected in each sample analyzed. The statistical results were grouped by principal components analysis, to better understand the profile of the seized samples. CONCLUSION: This work successfully established a fast and simple method for determination of AAS and can be applied to verify the profile of seized samples.
Assuntos
Congêneres da Testosterona/química , Acetonitrilas , Espectrometria de Massas , Preparações Farmacêuticas , Testosterona , ÁguaRESUMO
A set of synthetic data, of antibacterial evaluation against gram-positive bacteria, as well as, the interaction of bacterial with lipid-core nanocapsules containing fusidic acid is presented here. In this data set, the analytical data are detailed; serial microdilution; nanoparticle tracking analysis; transmission electron microscopy; minimum inhibitory concentration; diameter size and zeta potential, and infra-red of the formulations before and after contact with bacteria.
RESUMO
RESUMO O plantão psicológico é uma modalidade de atenção clínica em psicologia que disponibiliza atendimentos imediatos sem restrição de demanda. Ainda, o trabalho especializado oferecido pelo psicólogo consegue identificar os recursos pessoais do cliente para lidar com sua demanda e promover sua saúde sem necessidade de assistência intensiva. Para os demais casos, encaminhamentos e orientações permitem acionar outros serviços apropriados. Este trabalho teve como objetivo identificar e compreender as intervenções empregadas por um plantonista. A partir de análise de conteúdo de registros documentais de seis casos atendidos na modalidade de plantão psicológico realizado em uma clínica-escola e utilizando as matrizes teóricas da psicologia humanista-fenomenológica, foram identificadas e discutidas três unidades significativas a respeito das intervenções empregadas, nomeadas de reflexão, cuidado e explicação. Foi possível, então, relacionar as intervenções a uma facilitação de processo terapêutico e de ajuda ao cliente, encaminhando-o para um posicionamento mais pessoal e consciente. Houve a configuração de um ambiente de empatia e de aceitação incondicional em que os afetos puderam ser recebidos pelo plantonista com uma postura coerente e sensível. Somado a isso, foi possível desenvolver uma relação de aproximação entre o cliente e suas experiências, favorecendo ressignificações e maior consciência sobre seus modos de estar no mundo, logo uma condição mais autônoma e autêntica de existência. Por fim, algumas contribuições foram apresentadas e alguns temas centrais problematizados para dar corpo e movimento às pesquisas acerca do plantão psicológico.
RESUMEN La guardia psicológica es una modalidad de atención clínica en psicología que ofrece atendimientos inmediatos sin restricción de demanda. Además, el trabajo especializado ofrecido por el psicólogo logra identificar los recursos personales del cliente para lidiar con su demanda y promover su salud sin necesidad de asistencia intensiva. Para los demás casos, las remisiones y las orientaciones permiten accionar otros servicios apropiados. En esta investigación se tuvo como objetivo identificar y entender las intervenciones empleadas por un psicólogo de guardia. A partir de análisis de contenido de registros documentales de seis casos atendidos en la modalidad de guardia psicológica realizado en una escuela clínica y utilizando el enfoque de la psicología humanista-fenomenológica, fueron identificadas y discutidas tres unidades significativas respecto de las intervenciones empleadas, denominadas de reflexión, cuidado y explicación. Es posible, entonces, relacionar las conductas a una facilitación de proceso terapéutico y de ayuda al cliente, encaminándolo hacia un posicionamiento más personal y consciente. Hubo la configuración de un ambiente de empatía y de consideración positiva incondicional en que los afectos pudieron ser recibidos por el psicólogo de guardia con una postura coherente y sensible. Al sumado a ello, fue posible desarrollar una relación de acercamiento entre el cliente y sus experiencias, favoreciendo resignificaciones y mayor conciencia sobre sus modos del estar en el mundo, luego una condición más autómata y auténtica de existencia. Por último, algunas contribuciones fueron presentadas y algunos temas centrales problematizados para dar cuerpo y movimiento a las investigaciones acerca de la guardia psicológica.
ABSTRACT Psychological duty is a modality of clinical attention in psychology that makes available immediate appointments without restriction of requests. In addition, the specialized work offered by the psychologist is able to identify the personal resources of the client in order to deal with their request, and to promote their health without the need for intensive care. For the balance of the other cases, referral reports and guidance enable the activation of other appropriate services. This work aimed to identify and to understand the interventions employed by a psychologist on duty. Starting from the content cnalysis of records of six cases attended by the psychological duty schedule performed in a school-clinic, and by the use of the humanistic-phenomenological approach in psychology, three categories were identified and discussed regarding the interventions employed, namely reflections, care, and explanation. Thus, it was possible to relate the actions to a facilitator of the therapeutic process and help the attended person, leading them to a more personal and aware position. There is a setting of an empathic environment, and of unconditional positive regard in which the affections could be received by the psychologist on duty from a coherent and sensible posture. Added to this, it was possible to develop a proximity relationship between the attended person and their life experiences, favoring resignifications and a greater awareness of their ways of being in the world, so, a more autonomous and authentic condition of existence. Finally, some contributions were presented, and some core topics problematised in order to embody and give movement to the research about the psychological duty.
Assuntos
Humanos , Masculino , Feminino , Psicologia Clínica/métodos , Condutas Terapêuticas Homeopáticas , Pacotes de Assistência ao Paciente/psicologia , Psicologia , Afeto , Plantão Médico , Recursos em Saúde , Acontecimentos que Mudam a VidaRESUMO
OBJECTIVE: To evaluate the accuracy of percutaneous transhepatic biliary biopsy (PTBB) in patients with suspected biliary obstruction. MATERIALS AND METHODS: This was a retrospective analysis of 18 patients with obstructive jaundice who underwent PTBB. In each patient, three to ten fragments were collected from the lesion. The final diagnosis was confirmed in the pathology report. We also reviewed analyses of the results of laboratory tests performed before the procedure, as well as the Bismuth classification, clinical outcome, complications occurring during the procedure, access route, and materials used. RESULTS: Technical success was achieved in 100% of the PTBB procedures. Among the 18 patients clinically diagnosed with bile duct stenosis, the pathological analysis confirmed that diagnosis in 17. In one case, the pathological findings were considered false-negative. The predominant tumor was cholangiocarcinoma (seen in 50% of the cases). Sixteen of the procedures (88.9%) were performed without complications. Transient hemobilia occurred in one case, and cholangitis occurred in another. CONCLUSION: PTBB is a safe, viable, simple technique with a high rate of true-positive results for the definitive diagnosis of obstructive jaundice.
OBJETIVO: Avaliar a precisão diagnóstica da colangiobiópsia trans-hepática percutânea (CBTP) em pacientes com suspeita de obstrução biliar. MATERIAIS E MÉTODOS: Análise retrospectiva de 18 pacientes apresentando icterícia obstrutiva foram submetidos a CBTP. Em cada paciente, 3 a 10 fragmentos foram coletados da lesão. O diagnóstico final foi confirmado por relatório anatomopatológico. Adicionalmente, foram registrados a análise laboratorial antes do procedimento, a classificação de Bismuth, o desfecho clínico, as intercorrências durante o procedimento, a via de acesso e os materiais utilizados. RESULTADOS: A CBTP apresentou sucesso técnico em 100% dos casos. Dos 18 pacientes clinicamente diagnosticados com estenose biliar, 17 receberam diagnóstico patológico positivo. Em um caso os achados patológicos foram considerados falso-negativos. O colangiocarcinoma foi a neoplasia predominante (50%). Dezesseis (88,9%) procedimentos foram realizados sem intercorrências. Hemobilia transitória ocorreu em um caso e colangite em outro caso isolado. CONCLUSÃO: A CBTP é uma técnica segura, viável e simples, com alta taxa de verdadeiro-positivos para o diagnóstico definitivo de causas de icterícia obstrutiva.
RESUMO
Abstract Objective: To evaluate the accuracy of percutaneous transhepatic biliary biopsy (PTBB) in patients with suspected biliary obstruction. Materials and methods: This was a retrospective analysis of 18 patients with obstructive jaundice who underwent PTBB. In each patient, three to ten fragments were collected from the lesion. The final diagnosis was confirmed in the pathology report. We also reviewed analyses of the results of laboratory tests performed before the procedure, as well as the Bismuth classification, clinical outcome, complications occurring during the procedure, access route, and materials used. Results: Technical success was achieved in 100% of the PTBB procedures. Among the 18 patients clinically diagnosed with bile duct stenosis, the pathological analysis confirmed that diagnosis in 17. In one case, the pathological findings were considered false-negative. The predominant tumor was cholangiocarcinoma (seen in 50% of the cases). Sixteen of the procedures (88.9%) were performed without complications. Transient hemobilia occurred in one case, and cholangitis occurred in another. Conclusion: PTBB is a safe, viable, simple technique with a high rate of true-positive results for the definitive diagnosis of obstructive jaundice.
Resumo Objetivo: Avaliar a precisão diagnóstica da colangiobiópsia trans-hepática percutânea (CBTP) em pacientes com suspeita de obstrução biliar. Materiais e Métodos: Análise retrospectiva de 18 pacientes apresentando icterícia obstrutiva foram submetidos a CBTP. Em cada paciente, 3 a 10 fragmentos foram coletados da lesão. O diagnóstico final foi confirmado por relatório anatomopatológico. Adicionalmente, foram registrados a análise laboratorial antes do procedimento, a classificação de Bismuth, o desfecho clínico, as intercorrências durante o procedimento, a via de acesso e os materiais utilizados. Resultados: A CBTP apresentou sucesso técnico em 100% dos casos. Dos 18 pacientes clinicamente diagnosticados com estenose biliar, 17 receberam diagnóstico patológico positivo. Em um caso os achados patológicos foram considerados falso-negativos. O colangiocarcinoma foi a neoplasia predominante (50%). Dezesseis (88,9%) procedimentos foram realizados sem intercorrências. Hemobilia transitória ocorreu em um caso e colangite em outro caso isolado. Conclusão: A CBTP é uma técnica segura, viável e simples, com alta taxa de verdadeiro-positivos para o diagnóstico definitivo de causas de icterícia obstrutiva.