Use of choline chloride-D-sorbitol deep eutectic solvent as additive in cyclodextrin-electrokinetic chromatography for the enantiomeric separation of lacosamide

The potential of chiral deep eutectic solvents to enhance the chiral discrimination in Cyclodextrin-Electrokinetic Chromatography is demonstrated in this work. With this aim, a method enabling the enantiomeric separation of the antiepileptic drug lacosamide was developed. After a screening using 12 cyclodextrin derivatives, succinyl-B-CD was chosen due to its higher discrimination power to separate lacosamide enantiomers. The effect of different variables, such as cyclodextrin concentration, buffer concentration, temperature and separation voltage, on the enantiomeric separation of lacosamide, was studied. As the maximum enantiomeric resolution achieved under the optimized conditions was lower than 1.5, the effect of the addition of methanol or different deep eutectic solvents (choline chloride - ethylene glycol, choline chloride - urea, choline chloride - D-glucose, and choline chloride - D-sorbitol) as additives to the separation medium was investigated. The best results in terms of enantiomeric resolution and analysis time were obtained using choline chloride - D-sorbitol at a 0.5 % (w/v) in a 100 mM borate buffer (pH 9.0) with 18 mM succinyl-B-CD. Under these conditions, lacosamide enantiomers were separated with a resolution value of 2.8. Analytical characteristics of the developed method were evaluated and demonstrated to be adequate to apply the methodology to the enantiomeric analysis of lacosamide in a pharmaceutical formulation

Enantiomeric analysis of pyrethroids and organophosphorus insecticides

The use of pesticides has increased sharply in the last decades, not only in agriculture, but also in industry, public health, and other areas. Pyrethroids and organophosphorus insecticides are among the most employed pesticides. These chemicals usually contain asymmetric chiral atoms; thus, they are characterized by stereoisomerism. Although most of these chiral pesticides are produced, used, and released as racemic mixtures, the different enantiomers of these compounds can present different insecticidal activity, different toxicity against vertebrates and invertebrates, and also different persistence in the environment. In fact, in some cases, only one enantiomer is active, while the other can be less active or even toxic to non-target organisms. Therefore, the development of enantioselective analytical methodologies enabling their determination presents a high interest. Different separation techniques, including high performance liquid chromatography, gas chromatography, supercritical fluid chromatography, and capillary electrophoresis, have been employed to achieve the chiral analysis of pyrethroids and organophosphorus insecticides. This review presents the characteristics of the stereoselective analytical methodologies developed with this aim from 2010 to April 2019 and their applications to the analysis of real samples as well as for toxicity and biodegradation studies

Modeling-based optimization of the simultaneous enantiomeric separation of multicomponent mixtures of phenoxy acid herbicides using dual cyclodextrin systems by Capillary Electrophoresis

In this work, the Dubsky's model proposed for Capillary Electrophoresis (CE) enantioseparation systems with a mixture of chiral selectors was applied to the rapid optimization of the simultaneous enantiomeric separation of a multicomponent mixture of six phenoxy acid herbicides using a dual system of two cyclodextrins (CDs), (2-hydroxypropyl)-beta-CD (HP-beta-CD) and heptakis(2,3,6-tri-O-methyl)-beta-CD (TM-beta-CD). Simply by carrying out a small number of individual experiments separately with each CD, the Dubsky's model enabled to foresee the results that could be obtained for any possible combination of concentrations and relative proportion of both CDs in the mixture. Results obtained in this work demonstrated that the model was successful by improving the previous results experimentally obtained by the trial and error method for the simultaneous enantiomeric separation of the six phenoxy acid herbicides studied in this work. In fact, the separation was improved in terms of enantiomeric resolutions obtained (from 1.2 to 4.2 for concentrations of CDs of 4 mM HP-beta-CD and 16 mM TM-beta-CD) and by considerably reducing the time to optimize the separation conditions enabling to find, in a faster and efficient way, the most adequate proportion of both CDs and the concentration of each CD in the mixture to obtain baseline separation of the twelve enantiomers. Additionally, the apparent complexation constants between enantiomers and each CD were calculated. This is the first time that the above-mentioned model was applied to a multicomponent mixture of chiral compounds. (C) 2019 Elsevier B.V. All rights reserved

Enantiomeric determination of drugs in pharmaceutical formulations and biological samples by Electrokinetic Chromatography

Chirality is a relevant issue in the pharmaceutical field due to the different biological activity that enantiomers of a chiral drug can show. In fact, the desired biological or pharmaceutical activity might be present in only one of the enantiomers, while the other enantiomer(s) may have different biological activity, be inactive or even toxic. This has motivated in recent years the development of drugs marketed as pure enantiomers to avoid exposing the organism to the action of enantiomers that may not be active or even harmful to health. Thus, it is of high interest to develop enantioselective analytical methodologies to control the presence of enantiomeric impurities and to understand the enantioselective metabolism of chiral drugs. This review gives an overview about the analytical strategies developed by electrokinetic chromatography (EKC) from 2010 to June 2019 for the enantiomeric determination of drugs in both pharmaceutical formulations and biological samples. The types of chiral selectors used, the migration order of enantiomers, their resolution, the detection technique employed and the sensitivity achieved are revised and compared. Also, applications to assess the enantiomeric purity control of pharmaceutical formulations and to determine chiral drugs in biological samples to study their metabolism are included. Advantages and limitations of the chiral methods developed by EKC are also discussed

Aprendiendo mucho en muy poco tiempo -SFA y opresión-

Presentamos la experiencia de innovación docente desarrollada en la asignatura de Orientación Psicoeducativa, fundamentada en la metodología de Sensibilización-Formación y Acción. La actividad llevada a cabo ha sido evaluada mostrando como en el periodo de dos semanas los estudiantes han pasado de no saber nada respecto al análisis de un caso de opresión, a organizar debates y adquirir unos conocimientos que los han sorprendido hasta a ellos mismos. Los resultados son analizados desde cómo se mejora la percepción de la opresión, mejora la empatía y el empoderamiento del alumnado.We are introducing an innovative teaching experience developed in the course in Psycho-educational Guidance, based on the methodology of training and awareness-Action. The activity has been carried out showing assessed as in the period of two weeks students have gone from not knowing anything about the analysis of a case of oppression, to organize discussions on it and acquire knowledge that have surprised even themselves. The results are analyzed from how the perception of oppression is improved, enhancing empathy and empowerment of students

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: A nationwide study in Spain

Objective To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. Settings The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. Participants This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. Interventions An exploratory factorial analysis was performed to select the most relevant variables of the sample. Primary and secondary outcome measures Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. Results Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/10 5 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade =3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/10 5 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. Conclusions Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/10 5 people/week) was a statistically independent predictor of mortality. Trial registration number CEIM 20/217

Enantiomeric separation of colchicine and lacosamide by nano-LC. Quantitative analysis in pharmaceutical formulations

A chiral analytical methodology was developed by nano-liquid chromatography (nano-LC) enabling the enantiomeric separation of two chiral drugs, lacosamide (novel antiepileptic drug) and colchicine (antiuremic drug), commercialized as pure enantiomers. A capillary column lab-packed with an amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phase was used in a lab-assembled nano-LC system. Lacosamide and colchicine enantiomers were separated in less than 8.0 and 9.0 min, respectively, with resolution values of 1.6 and 2.3, using 20 nL of sample and 1.8 mu L of mobile phase per analysis. The analytical characteristics of the proposed methodology were evaluated according to the International Council for Harmonisation (ICH) guidelines, showing good analytical performance with good recoveries (97-98% and 100-103%) and precision values (relative standard deviation (RSD) <10.5 and <3.0%) for lacosamide and colchicine enantiomers, respectively. LODs were 1.7 and 2.0 mu g/mL for (S)- and (R)-lacosamide, respectively, and 1.0 mu g/mL for both colchicine enantiomers. Additionally, the developed methodology enabled to detect a 0.1% of the enantiomeric impurities, fulfilling the ICH regulation requirements. The method was applied to the determination of lacosamide and colchicine enantiomers in different pharmaceutical formulations to ensure their quality control. The content of the enantiomeric impurities was below a 0.1% and the amount of (R)-lacosamide and (S)-colchicine agreed with their labeled contents