Characterization of 2,3-diarylxanthones by electrospray mass spectrometry: gas-phase chemistry versus known antioxidant activity properties

Xanthones (XH) are a class of heterocyclic compounds widely distributed in nature that hold numerous noteworthy biological and antioxidant activities. Therefore, it is of utmost importance to achieve relevant detailed structural information to understand and assist prediction of their biological properties. The potential relationship between radical-mediated xanthone chemistry in the gas phase and their promising antioxidant activities has not been previously explored.Thanks are due to Fundação para a Ciência e Tecnologia (FCT, Portugal), European Union, QREN, FEDER and COMPETE, for funding the QOPNA research unit (project PEst-C/QUI/UI0062/2013; FCOMP-01-0124-FEDER-037296), and the Portuguese National Mass Spectrometry Network, RNEM (REDE/1504/REM/2005). E. M. P. Silva is also grateful to FCT (ref SFRH/BPD/66961/2009) for a Post-Doc grant.info:eu-repo/semantics/publishedVersio

Analytical methods for quantification of tranexamic acid in biological fluids: A review

Tranexamic acid (TXA) is a synthetic derivative of the amino acid lysine with antifibrinolytic properties. There is still a lack of pharmacokinetic and pharmacodynamic data concerning variable age groups undergoing surgeries with high blood loss. The optimum dose and administration schedules of TXA are still subject of research, aiming at a safe inhibition of fibrinolysis in the perioperative period. Hence, effective methods for determination of TXA in biological samples are needed. The aim of this review is to discuss the required sample treatment procedures and the analytical methods applied for quantification of TXA, focusing on selected derivatisation agents and internal standards. Methods comprising a separative step (GC, LC or CZE) coupled to spectrophotometric, fluorimetric and mass spectrometry detection were considered, showing a tendency for implementation of MS/MS methods in more recent reports. Detection limits ranging from 0.01 to 0.5 μg mL− 1 in blood plasma were so far attained using LC-MS/MS.info:eu-repo/semantics/publishedVersio

Determination of tranexamic acid in human plasma by UHPLC coupled with tandem mass spectrometry targeting sub-microgram per milliliter levels

Tranexamic acid (TXA) is an antifibrinolytic drug, with the ability to inhibit lysine binding at plasminogen receptors, used in adult trauma patients with on-going or at risk of significant haemorrhage. To understand the pharmacokinetics and pharmacodynamics of this drug in variable age groups undergoing surgeries with high blood loss, effective methods for determination of TXA in biological samples at sub-μg mL−1 are still required. We describe herein the development and validation of a method based on ultra-high performance liquid chromatography coupled to triple quadrupole-tandem mass spectrometry to quantify TXA in human plasma. An inexpensive, simple and efficient sample clean-up was implemented, not requiring matrix-matching calibration. Sample preparation consisted in protein precipitation using acetonitrile containing 0.5% (v/v) formic acid, followed by hydrophilic interaction based chromatographic separation, with elution in isocratic mode using a combination of acetonitrile and water (75:25, v/v), with quantification of TXA based on selected reaction monitoring. Good linearity was achieved (r2 > 0.997) for TXA concentrations ranging from 30 to 600 ng mL−1, with LOD of 18 ng mL−1 in plasma. The developed method proved to be selective, sensitive, accurate (96.4–105.7% of nominal values) and precise (RSD ≤ 4.5%). TXA was found to be stable in plasma extracts standing 24 h at room temperature (20 °C) or in the autosampler, and after three freeze-thawing cycles. Mean recovery values of TXA spiked plasma samples were ≥91.9%. No significant matrix effects were observed. The proposed methodology was successfully applied to the clinical study of plasma samples recovered during scoliosis surgery of pediatric patients pretreatment with TXA.info:eu-repo/semantics/publishedVersio

Melhor evidência científica na prevenção das quedas em idosos institucionalizados

A questão das quedas em idosos constitui um problema de saúde pública. Objetivo: Verificar se a prática de atividade física, em comparação com a não prática de atividade física, fornece melhor evidência para prevenir quedas em idosos que estão institucionalizados. Metodologia: Realizou-se uma revisão sistemática da literatura de acordo com a metodologia Problema, Intervenção, Comparação e Outcomes. Selecionaram-se 44 artigos na plataforma Web of Science dos quais resultaram, para análise final 9, segundo os critérios de inclusão definidos. Para atestar da qualidade dos estudos e classificação dos níveis de evidência aplicou-se a escala Oxford Centre for Evidence-Based Medicine. A seleção dos estudos e a extração dos dados foi realizada por dois revisores. Resultados: A evidência científica encontrada foi de alta qualidade resultando em estudos maioritariamente de nível I e II. Dos 9 artigos, 55% evidenciam que a atividade física diminuiu a prevalência de quedas em idosos institucionalizados, quando comparada com a não atividade física. Há evidência de que os programas de exercícios para prevenir as quedas em idosos reduzem a prevalência e evitam lesões decorrentes das mesmas. Assim, muitos dos fatores de risco para quedas são passíveis de serem corrigidos através de bons programas de exercícios. Conclusões: Os estudos revelam que praticar exercício físico contribui para melhorar a capacidade funcional dos idosos e resulta em protecção relativamente às quedas. Assim, sugere-se que existam equipas multidisciplinares que incentivem a atividade física quer nas instituições quer na comunidade. Um protocolo, simples e de baixo custo poderá ser aplicado em instituições.info:eu-repo/semantics/publishedVersio

Flow-based bioconjugation of coumarin phosphatidylethanolamine probes:Optimised synthesis and membrane molecular dynamics studies

A series of phosphatidylethanolamine fluorescent probes head-labelled with 3-carboxycoumarin was prepared by an improved bioconjugation approach through continuous flow synthesis. The established procedure, supported by a design of experiment (DoE) set-up, resulted in a significant reduction in the reaction time compared to the conventional batch method, in addition to a minor yield increase. The characterization of these probes was enhanced by an in-depth molecular dynamics (MD) study of the behaviour of a representative probe of this family, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine labelled with 3-carboxycoumarin (POPE-COUM), in bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine (SLPC) 2:1, mimicking the composition of the egg yolk lecithin membranes recently used experimentally by our group to study POPE-COUM as a biomarker of the oxidation state and integrity of large unilamellar vesicles (LUVs). The MD simulations revealed that the coumarin group is oriented towards the bilayer interior, leading to a relatively internal location, in agreement with what is observed in the nitrobenzoxadiazole fluorophore of commercial head-labelled NBD-PE probes. This behaviour is consistent with the previously stated hypothesis that POPE-COUM is entirely located within the LUVs structure. Hence, the delay on the oxidation of the probe in the oxygen radical absorbance capacity (ORAC) assays performed is related with the inaccessibility of the probe until alteration of the LUV structure occurs. Furthermore, our simulations show that POPE-COUM exerts very little global and local perturbation on the host bilayer, as evaluated by key properties of the unlabelled lipids. Together, our findings establish PE-COUM as suitable fluorescent lipid analogue probes.</p

Fast monolith-based chromatographic method for determination of methotrexate in drug delivery studies

Methotrexate (MTX) is a derivative of aminopterin, used as an anticancer or an anti-inflammatory agent. The development of suitable drug delivery systems containing MTX is an active area of research, requiring suitable analytical methods. Therefore, a high-throughput HPLC method is proposed for determination of MTX in the delivery system and permeation studies. Chromatographic separation was achieved on a reversed phase monolithic C18 column using isocratic elution (phosphate buffer (pH 7.0, 10 mM)-ACN (91:9, v/v)) and spectrophotometric detection at 302 nm. Total run time was 3.5 min, with MTX retention time of 2.1 min, providing 17 determinations per hour. The method was found to be specific, accurate (99.2–110%) and precise for intra-day (RSD ≤ 3.5%) and inter-day assays (RSD ≤ 3.4%). MTX showed stability after 24 h at room temperature or in the autosampler (4 °C) and over three freeze-thaw cycles with recoveries ≥94.2%. The validated method was successfully applied to establish in vitro drug release profile of MTX delivered by lipid nanoparticles. Application to pig skin permeation media provided mean recovery values ranging from 94.1 to 101.6% (RSD ≤ 1.1%).info:eu-repo/semantics/publishedVersio

Characterization of Isomeric Cationic Porphyrins with β-Pyrrolic Substituents by Electrospray Mass Spectrometry: The Singular Behavior of a Potential Virus Photoinactivator

Electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (ESI-MS/MS) have been used to differentiate the 2- and 4-methylpyridyl isomers of free-base and metallated cationic β-vinylpyridylporphyrins. The analysis by ESI-MS/MS of the deuterated analogs and semiempirical calculations of structural and electronic parameters were also undertaken. The two free-base isomers are easily differentiated by ESI-MS/MS but the presence of a metallic center renders differentiation of the metallated isomers less effective. The data acquired show that of all the studied compounds, the free-base 2-methylpyridyl isomer, which was operative in the in vitro photoinactivation of Herpes simples virus, has a different gas-phase behavior. Local distortion of the macrocycle due to the presence of the β-vinylpyridyl substituent occurs for all the compounds, but a different electron density distribution can account for the observed gas-phase behavior of this potential virus photoinactivator