Chiral micellar electrokinetic chromatography

The potential of Micellar Electrokinetic Chromatography to achieve enantiomeric separations is reviewed in this article. The separation principles and the most frequently employed separation strategies to achieve chiral separations by Micellar Electrokinetic Chromatography are described. The use of chiral micellar systems alone or combined with other micellar systems or chiral selectors, as well as of mixtures of achiral micellar systems with chiral selectors is discussed together with the effect of different additives present in the separation medium. Indirect methods based on the derivatization of analytes with chiral derivatizing reagents and the use of achiral micelles are also considered. Preconcentration techniques employed to improve sensitivity and the main approaches developed to facilitate the coupling with Mass Spectrometry are included. The most recent and relevant methodologies developed by chiral Micellar Electrokinetic Chromatography and their applications in different fields are presented

Enantiomeric determination of econazole and sulconazole by electrokinetic chromatography using hydroxypropyl-b-cyclodextrin combined with ionic liquids based on L-lysine and Ly-glutamic acid

Two analytical methodologies based on the combined use of hydroxypropyl-beta-cyclodextrin and two different amino acid-based chiral ionic liquids (tetrabutylammonium-L-lysine or tetrabutylammonium-L-glutamic acid) in electrokinetic chromatography were developed in this work to perform the enantios-elective determination of econazole and sulconazole in pharmaceutical formulations. The influence of different experimental variables such as buffer concentration, applied voltage, nature and concentration of the ionic liquid, temperature and injection time, on the enantiomeric separation was investigated. The combination of hydroxypropyl-beta-cyclodextrin and tetrabutylammonium-L-lysine under the optimized conditions enabled to achieve the enantiomeric determination of both drugs with high enantiomeric resolution (3.5 for econazole and 2.4 for sulconazole). The analytical characteristics of the developed methodologies were evaluated in terms of linearity, precision, LOD, LOQ and recovery showing good performance for the determination of both drugs which were successfully quantitated in pharmaceutical formulations. This work reports the first analytical methodology enabling the enantiomeric determination of sulconazole in pharmaceutical formulations

A chiral electrokinetic chromatography method for the separation and quantitation of licarbazepine and licarbazepine acetate in pharmaceutical formulations and urine samples

S-Licarbazepine acetate is a new antiepileptic that is quickly metabolized to S-licarbazepine which is the active principle. In this study, an enantioselective methoddology enabling the simultaneous separation of licarbazepine acetate and licarbazepine by Electrokinetic Chromatography has been developed for the first time. After evaluating the potential of different chiral selectors, including bile salts and cyclodextrins, and selecting carboxymethyl-?-cyclodextrin as the most appropriate, a Box-Behnken experimental design was effectively applied for the optimization of the experimental separation conditions. Employing the best conditions, the four enantiomers were simultaneously separated (resolution values > 2.4) in less than 7 min. The evaluation of the figures of merit of the developed methodology showed to be suitable to determine both compounds. Finally, the EKC method was successfully applied in three different studies: (i) the quality control of the enantiopure pharmaceutical formulation, (ii) the monitoring of the stability and gastrointestinal digestion of the pharmaceutical formulation through a hydrolysis study, and (iii) the determination of licOH enantiomers in urine samples

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

Advances in the determination of non-protein amino acids in foods and biological samples by capillary electrophoresis

There are hundreds of non-protein amino acids whose importance in food and biological matrices is still unknown. Many of these compounds mainly exist in food as products formed during food processing, as metabolic intermediates or as additives to increase nutritional and functional properties of food. Moreover, they have also demonstrated to play an important role in the pharmaceutical and clinical fields since they may be used therapeutically in the treatment of some pathologies and their levels may be related with some diseases. For this reason, the analysis of non-protein amino acids may provide relevant information in the food and biological fields. This article reviews the most recent advances in the development of analytical methodologies employing capillary electrophoresis for the achiral and chiral analysis of non-protein amino acids in food and biological samples. With this aim, the most relevant information concerning the separation and detection of these compounds by capillary electrophoresis is discussed and detailed experimental conditions under which their determination was achieved in food and biological samples are given covering the period of time from 2015 to 2018

Glucose homeostasis changes and pancreatic β-cell proliferation after switching to cyclosporin in tacrolimus-induced diabetes mellitus

AbstractBackgroundSwitching to cyclosporin A may result in a reversion of tacrolimus-induced diabetes mellitus. However, mechanisms underlying such a reversion are still unknown.MethodsObese Zucker rats were used as a model for tacrolimus-induced diabetes mellitus. A cohort of 44 obese Zucker rats received tacrolimus for 11 days (0.3mg/kg/day) until diabetes development; then, (a) 22 rats were euthanized at day 12 and were used as a reference group (tacrolimus-day 12), and (b) 22 rats on tacrolimus were shifted to cyclosporin (2.5mg/kg/day) for 5 days (tacrolimus-cyclosporin). An additional cohort of 22 obese Zucker rats received the vehicle for 17 days and was used as a control group. All animals underwent an intraperitoneal glucose tolerance test at the end of the study.Resultsβ-Cell proliferation, apoptosis and Ins2 gene expression were evaluated. Compared to rats in tacrolimus-day 12 group, those in tacrolimus-cyclosporin group showed a significant improvement in blood glucose levels in all assessment points in intraperitoneal glucose tolerance test. Diabetes decreased from 100% in tacrolimus-day-12 group to 50% in tacrolimus-cyclosporin group. Compared to tacrolimus-day-12 group, rats in tacrolimus-cyclosporin group showed an increased β-cell proliferation, but such an increase was lower than in rats receiving the vehicle. Ins2 gene expressions in rats receiving tacrolimus-cyclosporin and rats receiving the vehicle were comparable.ConclusionAn early switch from tacrolimus to cyclosporin in tacrolimus-induced diabetes mellitus resulted in an increased β-cell proliferation and reversion of diabetes in 50% of cases

New-onset atrial fibrillation during COVID-19 infection predicts poor prognosis

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led toa paradigm shift in healthcare worldwide. Little is known about the impact on the cardiovascularsystem, and the incidence and consequences of new onset of atrial fibrillation (AF) in infected patientsremain unclear. The aim of this study was to analyze the cardiovascular outcomes of patients with newonset AF and coronavirus disease 2019 (COVID-19) infection.Methods: This observational study analyzed a sample of 160 consecutive patients hospitalized due toCOVID-19. A group with new-onset AF (n = 12) was compared with a control group (total: n = 148,sinus rhythm: n = 118, previous AF: n = 30). New-onset AF patients were significantly older andhypertensive, as well as presenting more frequently with a history of acute coronary syndrome andrenal dysfunction. This group showed a higher incidence of thromboembolic events (41.7% vs. 4.1%;p < 0.001), bleeding (33.3% vs. 4.7%, p = 0.005), a combined endpoint of thrombosis and death(58.3% vs. 19.6%, p = 0.006) and longer hospital stays (16.4 vs. 8.6 days, p < 0.001), with no differences in all-cause mortality.Results: In multivariate analysis, adjusted by potential confounding factors, new-onset AF demonstrateda 14.26 odds ratio for thromboembolism (95% confidence interval 2.86–71.10, p < 0.001).Conclusions: New-onset AF in COVID-19 patients presumably has a notable impact on prognosis.The appearance of new-onset AF is related to worse cardiovascular outcomes, considering it as an independent predictor of embolic events. Further studies are needed to identify patients with COVID-19at high risk of developing “de novo” AF, provide early anticoagulation and minimize the embolic risk ofboth entities

Autologous Platelet-Rich Plasma in the Treatment of Perianal Fistula in Crohn’s Disease

[Aim] To assess clinical healing in patients with perianal Crohn’s disease with local intrafistular injection of autologous platelet-rich plasma.[Method] The pilot study was conducted at a single centre between January 2013 and December 2015. Autologous platelet-rich plasma was prepared in platelet-rich and platelet-poor fractions for local intrafistular injection in patients with proven, established perianal Crohn’s disease. Patients were permitted biological therapies, and the Perianal Crohn’s Disease Activity Index was recorded. Patients were followed for 48 weeks for clinical signs of healing (complete, partial or non-healing), monitoring fistula drainage, closure and epithelialization.[Results] The study included 29 patients (19 males; mean age 38 ± 12.8 years) with four exclusions in the operating room because surgery was not indicated and four lost to follow-up. Five adverse events were recorded, with two requiring the drainage of abscess collections. Of the 21 patients assessable at 24 weeks, there was complete healing, partial healing and non-healing in 7 (33.3%), 8 (38.1%) and 6 (28.6%) patients, respectively. By 48 weeks, there was complete healing, partial healing and non-healing in 6 (40%), 6 (40%) and 3 (20%) patients, respectively, with a reduction in the number of visible external fistula openings at both time points (P = 0.021). By the end of the study, there was a higher trend of healing if biological therapies were continued (85.7% with biologics vs. 75% without, P = 0.527), but there were no statistically significant differences and no differences in the Perianal Crohn’s Disease Activity Index.[Conclusion]Autologous platelet-rich plasma is safe in patients with perianal Crohn’s disease, with an acceptable healing rate over a medium-term follow-up, particularly if biological therapies are used concomitantly

Propuestas y perspectivas de investigación en el área de Didáctica de la Lengua y la Literatura: nuevos horizontes en la era de lo emocional y lo poscomunicativo

Innovation in Didactics of Language and Literature is the mail core of the present monographic edition