Simultaneous enantiomeric separation of carfentrazone-ethyl herbicide and its hydrolysis metabolite carfentrazone by cyclodextrin electrokinetic chromatography. Analysis of agrochemical products and a degradation study

The different activity and toxicity that the enantiomers of agrochemicals may have requires the development of stereoselective analytical methodologies enabling the individual determination of each enantiomer. The aim of this work was to develop the first Electrokinetic Chromatography methodology enabling the simultaneous enantiomeric separation of carfentrazone-ethyl erbicide and its hydrolysis metabolite carfentrazone. The use of an anionic cyclodextrin as chiral selector (captisol at 2.5% (w/v)) in a 25 mM acetate buffer, at a temperature of 30 ºC, and an applied voltage (reverse polarity) of -30 kV, allowed the simultaneous separation of the four enantiomers of the two compounds studied in 6.8 min with enantiomeric resolutions of 5.0 for carfentrazone-ethyl and 5.1 for carfentrazone. Analytical characteristics of the developed method were evaluated and found adequate to achieve the quantitation of carfentrazone-ethyl and carfentrazone. Analysis of a commercial herbicide formulation showed the potential of the method for the quality control of these agrochemical products. Degradation studies for carfentrazone-ethyl revealed that no significant degradation took place in cleaned sand samples while a significant but not stereoselective degradation took place in soils for the whole period of time considered (seven days)

Enantioseparation and ecotoxicity evaluation of ibrutinib by Electrokinetic Chromatography using single and dual systems

In this work, two chiral methods enabling the separation of ibrutinib enantiomers were developed by Electrokinetic Chromatography. A cyclodextrin (CD) or a mixture of the CD and a chiral ionic liquid (CIL) was used as chiral selector. Using the single CD system, seven neutral and six anionic CDs were tested in a formate buffer at pH 3.0 working in positive and negative polarity, respectively. The use of sulfated-?-CD (S-?-CD) and negative polarity originated the best results considering analysis time and enantioresolution. The optimization of the experimental conditions allowed obtaining the separation of ibrutinib enantiomers in an analysis time of 4.2 min with an enantioresolution value of 1.5. The effect of the addition of fifteen CILs on the enantioresolution was evaluated showing that both analysis time and enantioresolution were generally increased. A mixture of S-?-CD and [TMA][L-Lys] was selected which provided the separation of ibrutinib enantiomers in 8.1 min with an enantioresolution value of 3.3 under the same experimental conditions as in the case of using the single CD system. The enantiomeric impurity (S-ibrutinib) was the first-migrating isomer when using the single CD and the combined CD/CIL systems, as corresponds to the most desirable situation. Both chiral methods allowed the detection of the enantiomeric impurity up to a 0.1 % as established by the International Council on Harmonization. After establishing the analytical characteristics of both chiral methodologies developed, they were applied to the enantiomeric determination of ibrutinib in a pharmaceutical formulation for hospital use marketed as pure enantiomer (R-ibrutinib) and to evaluate the stability and ecotoxicity of racemic ibrutinib and R-ibrutinib on Daphnia magna. The developed methodologies enabled, for the first time, the rapid chiral quantitation of ibrutinib in abiotic and biotic matrices

Lianas Suppress Seedling Growth and Survival of 14 Tree Species in a Panamanian Tropical Forest

Lianas are a common plant growth form in tropical forests, where they compete intensely with trees, decreasing tree recruitment, growth, and survival. If the detrimental effects of lianas vary significantly with tree species identity, as is often assumed, then lianas may influence tree species diversity and community composition. Furthermore, recent studies have shown that liana abundance and biomass are increasing relative to trees in neotropical forests, which will likely magnify the detrimental effects of lianas and may ultimately alter tree species diversity, relative abundances, and community composition. Few studies, however, have tested the responses of multiple tree species to the presence of lianas in robust, well‐replicated experiments. We tested the hypotheses that lianas reduce tree seedling growth and survival, and that the effect of lianas varies with tree species identity. We used a large‐scale liana removal experiment in Central Panama in which we planted 14 replicate seedlings of 14 different tree species that varied in shade tolerance in each of 16 80 × 80 m plots (eight liana‐removal and eight unmanipulated controls; 3136 total seedlings). Over a nearly two‐yr period, we found that tree seedlings survived 75% more, grew 300% taller, and had twice the aboveground biomass in liana‐removal plots than seedlings in control plots, consistent with strong competition between lianas and tree seedlings. There were no significant differences in the response of tree species to liana competition (i.e., there was no species by treatment interaction), indicating that lianas had a similar negative effect on all 14 tree species. Furthermore, the effect of lianas did not vary with tree species shade tolerance classification, suggesting that the liana effect was not solely based on light. Based on these findings, recently observed increases in liana abundance in neotropical forests will substantially reduce tree regeneration, but will not significantly alter tropical tree species diversity, relative abundance, or community composition

Simultaneous Enantiomeric Separation of Carfentrazone-Ethyl Herbicide and Its Hydrolysis Metabolite Carfentrazone by Cyclodextrin Electrokinetic Chromatography. Analysis of Agrochemical Products and a Degradation Study

The different activity and toxicity that the enantiomers of agrochemicals may have requires the development of stereoselective analytical methodologies enabling the individual determination of each enantiomer. The aim of this work was to develop the first Electrokinetic Chromatography methodology enabling the simultaneous enantiomeric separation of carfentrazone-ethyl herbicide and its hydrolysis metabolite carfentrazone. The use of an anionic cyclodextrin as chiral selector (captisol at 2.5% (w/v)) in a 25 mM acetate buffer, at a temperature of 30 °C, and an applied voltage (reverse polarity) of −30 kV, allowed the simultaneous separation of the four enantiomers of the two compounds studied in 6.8 min with enantiomeric resolutions of 5.0 for carfentrazone-ethyl and 5.1 for carfentrazone. Analytical characteristics of the developed method were evaluated and found adequate to achieve the quantitation of carfentrazone-ethyl and carfentrazone. Analysis of a commercial herbicide formulation showed the potential of the method for the quality control of these agrochemical products. Degradation studies for carfentrazone-ethyl revealed that no significant degradation took place in cleaned sand samples while a significant but not stereoselective degradation took place in soils for the whole period of time considered (seven days)

Modelling the simultaneous chiral separation of a group of chiral drugs by electrokinetic chromatography using mixtures of cyclodextrins

Two mixtures of neutral cyclodextrins (CDs) were used in Electrokinetic Chromatography (EKC) to model and optimize the simultaneous enantiomeric separation of a group of seven drugs. Heptakis(2,6-di-O-methyl)-beta-CD (DM-beta-CD) combined with methyl-gamma-CD (M-gamma-CD) or with carboxyethyl-gamma-CD (CE-gamma-CD) was employed in a 25 mM formate buffer at pH 3.0 to have the drugs studied positively charged. Dubsky's model was applied to calculate the enantiomer effective electrophoretic mobilities for each combination of CDs at different averaged molar fractions and total CDs concentrations. The most adequate averaged molar fraction and total CDs concentration in terms of the simultaneous enantiomeric separation of the drug mixture were predicted by the model and results were experimentally corroborated. The model also foresaw interesting effects, derived from the combination of DM-beta-CD with M-gamma-CD or with CE-gamma-CD, on the individual chiral separation of some of the drugs studied. The observed reversal of the migration order for some compounds when changing the total CDs concentration was also predicted and the model showed its potential even at concentrations out of the experimental range of CD concentrations experimentally employed. The use of an averaged molar fraction of 0.8 for DM-beta-CD at a total CDs concentration of 40 mM in the DM-beta-CD/CE-gamma-CD system predicted by the model enabled the simultaneous enantiomeric separation of six of the drugs studied (except verapamil) with resolutions ranging from 0.6 to 4.0

Exploring the Potential of Microextraction in the Survey of Food Fruits and Vegetable Safety

The increasing demand for food to feed an exponentially growing population, the fast evolution of climate changes, how global warming affects soil productivity, and the erosion of arable lands, create enormous pressure on the food chain. This problem is particularly evident for fresh fruits and vegetables that have a short shelf life. For this reason, food safety precautions are not always a priority and they are often overused to increase the productivity and shelf life of these food commodities, causing concerns among consumers and public authorities. In this context, this review discusses the potential of microextraction in comparison to conventional extraction approaches as a strategy to improve the survey of food safety requirements. Accordingly, selected examples reported in the literature in the last five years will focus on the detection and quantification of pesticides, antibiotics, hormones, and preservatives in fresh fruits and vegetables using different extraction approaches. Overall, the use of microextraction techniques to survey the presence of contaminants in the food chain is very advantageous, involving simpler and faster protocols, reduced amounts of solvents and samples, and consequently, reduced waste produced during analysis while conserving a high potential for automation. Additionally, this higher greener profile of the microextraction techniques will boost a progressive substitution of conventional extraction approaches by microextraction processes in most analytical applications, including the survey of food chain safety

Células neuronales derivadas de células madre pluripotentes humanas como plataforma relevante para la detección de fármacos en la enfermedad de Alzheimer

Extracellular amyloid-beta deposition and intraneuronal Tau-laden neurofibrillary tanglesare prime features of Alzheimer’s disease (AD). The pathology of AD is very complex and still notfully understood, since different neural cell types are involved in the disease. Although neuronalfunction is clearly deteriorated in AD patients, recently, an increasing number of evidences havepointed towards glial cell dysfunction as one of the main causative phenomena implicated in ADpathogenesis. The complex disease pathology together with the lack of reliable disease models haveprecluded the development of effective therapies able to counteract disease progression. The discoveryand implementation of human pluripotent stem cell technology represents an important opportunityin this field, as this system allows the generation of patient-derived cells to be used for diseasemodeling and therapeutic target identification and as a platform to be employed in drug discoveryprograms. In this review, we discuss the current studies using human pluripotent stem cells focusedon AD, providing convincing evidences that this system is an excellent opportunity to advance inthe comprehension of AD pathology, which will be translated to the development of the still missingeffective therapies.Instituto de Salud Carlos IIIFEDER PI18/01557, PI18/01556CIBERNED (CB06/05/1116 toAG and CB06/05/0094 to JV)Consejería de Economía y Conocimiento UMA18-FEDERJA-211, PY18-RT-223, US-1262