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

Cuatro miradas sobre el Valle de los Caídos

El Monumento de la Santa Cruz del Valle de los Caídos se aborda en este Trabajo Fin de Grado desde cuatro miradas que son, a su vez, cuatro interrogantes: ¿Dónde está? ¿Cuál es su futuro? ¿Qué significa? ¿A quién pertenece? Estas cuestiones son la base de un análisis que planteamos como replicable para comprender cualquier monumento, porque abordan: 1.- el lugar de la edificación, con la fase de elección como especialmente significativa, y su influencia e imbricación en el monumento; 2.- sus posibilidades de futuro, consideradas también en el momento de la concepción, y la presencia significante del tiempo; 3.- el valor simbólico y referencial del conjunto y de sus elementos constitutivos; 4.- la importancia de la propiedad, que condiciona el resto de las cuestiones. El carácter de “lectura” de los “posibles lógicos del relato” que marcan los capítulos mencionados se subraya con la inclusión de un poema al principio de cada uno. El anteproyecto de Ley de Memoria Democrática redunda en la idea de que el relato sobre el Valle sigue abierto

Amino acid chiral ionic liquids combined with hydroxypropyl-beta-cyclodextrin for drug enantioseparation by capillary electrophoresis

Four amino acid chiral ionic liquids were evaluated in dual systems with hydroxypropyl-beta-cyclodextrin to investigate the enantioseparation by CE of a group of seven drugs as model compounds (duloxetine, verapamil, terbutaline, econazole, sulconazole, metoprolol, and nadolol). The use of two of these chiral ionic liquids (tetramethylammonium L-Lysine ([TMA][L-Lys]) and tetramethylammonium L-glutamic acid ([TMA][L-Glu]) as modifiers in CE is reported for the first time in this work whereas tetrabutylammonium L-lysine [TBA][L-Lys]) and tetrabutylammonium L-glutamic acid ([TBA][L-Glu]) were employed previously in CE although very scarcely. The effect of the nature and the concentration of each ionic liquid added to the separation buffer containing the neutral cyclodextrin on the enantiomeric resolution and the migration time obtained for each drug, was investigated. A synergistic effect was observed when combining each chiral ionic liquid with hydroxypropyl-beta-cyclodextrin in the case of the five compounds for which the cyclodextrin showed enantiomeric discrimination power when used as sole chiral selector (duloxetine, verapamil, terbutaline, econazole, sulconazole). Buffer concentration and pH, temperature and separation voltage were varied in order to optimize the enantiomeric separation of these five compounds using dual systems giving rise to resolutions ranging from 1.1 to 6.6. (C) 2019 Elsevier B.V. All rights reserved

Synthesis and characterization of carnitine-based ionic liquids and their evaluation as additives in cyclodextrin-electrokinetic chromatography for the chiral separation of thiol amino acids

In this study, new chiral ionic liquids based on the non-protein amino acid L-carnitine as cationic chiral counterpart and several anions (bis(trifluoromethane)sulfonimide (NTf2 -), L-lactate- or Cl-) as counterions were synthesized. Moreover, three different salts based on L-carnitine were also synthesized and the other three were commercially acquired and used for comparison. The synthesized ionic liquids and salts were characterized by nuclear magnetic resonance, fourier transform infrared spectroscopy, highperformance liquid chromatography-mass spectrometry, and elemental analysis. Subsequently, they were used as additives to establish a gamma-CD-based dual system for the enantiomeric separation of cysteine and homocysteine (previously derivatized with fluorenylmethoxycarbonyl chloride) by capillary electrokinetic chromatography. The effect of the nature of the anionic counterions and the presence of different substituents on the L-carnitine molecule on the chiral separation of both amino acids was investigated. The enantioseparations obtained with each dual system studied were compared in terms of the enantiomer effective mobilities (mu eff) and the effective electrophoretic selectivity (alpha eff). Practically, all the dual systems evaluated exhibited substantially improved enantioseparations for the two amino acids compared with the single gamma-CD syste