Additives In Capillary Electrophoresis Research Articles

New amphiphilic aminosaccharide derivatives as chiral selectors in capillary electrophoresis

Two amphiphilic aminosaccharide derivatives were investigated as chiral selector additives in capillary electrophoresis. Each substance has a glucosamine backbone carrying three hydrocarbon chains as the hydrophobic region and three carboxylic groups as the hydrophilic region, which is an artificial biologically active compound. Using each compound as a chiral selector, the optical resolution of dansylated amino acids or new quinolone antibacterial agents (NQs) was observed. Increasing the concentration of the chiral selector or the ionic strength of running solution led to successful optical resolution. In consideration of the chemical structure of each selector and the migration behavior of the enantiomers, the resolution seemed to be based on micellar electrokinetic chromatography mode. Both selectors differed in their enantioselectivity for dansylated amino acids or NQs although the chemical structures were similar.

Complexation of Voriconazole Stereoisomers with Neutral and Anionic Derivatised Cyclodextrins

A number of native, neutral derivatised and anionicderivatised cyclodextrins (CDs) were examined aschiral electrolyte additives in capillaryelectrophoresis (CE) to separate the fourstereoisomers of the new antifungal agent,voriconazole. A very large difference in interactionbetween each diastereoisomer and the CDs was observedin the CE study, where enantioselectivity was easilyobtained for one and extremely difficult to obtain forthe other. Nuclear magnetic resonance spectroscopy(1H-NMR) indicated a strong interaction betweenthe easily separated diastereoisomer and each of theCDs with enantiomeric shift nonequivalence values ofover 100 Hz obtained when using the anionicsulphobutylether-β-CD chiral solvating agent. Inaccordance with observations from the CE study, theopposite diastereoisomer indicated no shiftnonequivalence at all. The nature of the complexationbetween the easily separated diastereoisomer and theanionic sulphobutyletherβ-CD was also probedusing a two-dimensional nuclear Overhauser enhancementexperiment and a series of spin lattice relaxationtime measurements. It was found that theenantioselective interaction occurred through thepartial inclusion of a difluorophenyl group into theCD toroid which was also aided through a number ofadditional interactions between the drug molecule andthe sulphobutylether derivatives outside the CDtoroid.

Analysis of metal complexes in the presence of mixed ion pairing additives in capillary electrophoresis

It was demonstrated that metal complexes were successfully separated by capillary electrophoresis with mixed ion pairing agents in the running buffer. The migration behavior of metal complexes in the presence of the ionic additives ammonium, tetramethylammonium, tetraethylammonium, and tetrabutylammonium is discussed. 4-(2-Pyridylazo)resorcinol (PAR) was selected as the chelating reagent for the pre-column derivatization with Fe(II), Co(II), Ni(II), Cu(II) and Zn(II) ions. Under optimum conditions [10 m M NaH 2PO 4–Na 2HPO 4 as the running buffer containing 1·10 −4 M PAR, 5 m M tetramethylammonium and 5 m M tetrabutylammonium as the mixed ionic additives, pH 8.0, 70 cm (62.5 cm effective length)×50 μm capillary, separation voltage: 30 kV, injection time: 5 s, detection wavelength: 510 nm], the separation of six analytes was accomplished in 9 min. Excellent linearity with a dynamic range of two orders of magnitude from 1·10 −4 to 1·10 −6 M was obtained. The detection limits of Fe(II), Co(II), Ni(II), Cu(II) and Zn(II) were 6.80·10 −7, 3.36·10 −7, 3.27·10 −7, 2.64·10 −7 and 6.63·10 −7 M, respectively. This method was applied to the analysis of some metals in a pharmaceutical sample and an anode slime sample.

Semisynthetic chondroitins as chiral buffer additives in capillary electrophoresis

Chemically oversulfated galactosaminoglycans with potential as therapeutic agents (inhibitors of human leukocyte elastase) were tested as chiral selectors in capillary electrophoresis of basic racemates. The high anionic character of these compounds provides them with anodic mobility in acidic buffer; using uncoated capillaries, the enantioresolution of racemic basic drugs was obtained at pH 2.5. Dimethindene, chloroquine and chlorpheniramine were enantioresolved applying negative voltage (−15 kV) while the other analytes (propranolol, pindolol, tetrahydrozoline and cloperastine) exhibited catodic migration. The addition of organic solvents to the running buffer was evaluated in order to increase the resolution; methanol provides the best results and in general, baseline separation of the analytes was reached. The studied oversulfated mucopolysaccharide, shows the same ionic character of heparin but presents different stereochemistry and sites of sulfation. A comparison with heparin, used in the same acidic conditions, may underline the role of ionic, spatial and steric features of glycosaminoglycans in the enantiorecognition.

Chiral separations of indan, tetralin and benzosuberan derivatives by capillary electrophoresis

Several indan, tetralin and benzosuberan derivatives of diverse polarities were enantio-resolved by the use of sulfated β-cyclodextrins (CDs) or mixtures of sulfated β-CDs and γ-CD as chiral additives in capillary electrophoresis. Mixtures of sulfated β-CDs and hydroxypropyl β-CDs were also successfully utilized for enantiomeric and diastereomeric separations of some of the tetralin derivatives with two stereogenic centers. Both neutral and anionic analytes were resolved in the reversed electrophoretic polarity mode. Cationic amino derivatives of indan and tetralin were enantio-resolved in the conventional electrophoretic polarity mode.

Enantioseparation using selected polysaccharides as chiral buffer additives in capillary electrophoresis

Selected water-soluble, native polysaccharides – such as amylose, laminaran, pullulan – and derivatized polysaccharides – methyl cellulose, hydroxypropyl cellulose, and carboxymethyl amylose sodium salt (CM-Am) – were investigated as chiral selectors in capillary electrophoresis. Effects of degree of polymerization and concentration of amylose on the separation of enantiomers of 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate (BDHP) and a chiral cardiovascular drug cis-diltiazem were also studied. Pullulan and amyloses used in this study showed the same migration order for enantiomers of BDHP. In contrast, the migration order of BDHP enantiomers for cellulose derivatives and laminaran as well as with β-cyclodextrin was opposite to that for amylose and pullulan. The enantioseparation of several chiral drugs was also performed using high-molecular-mass amylose (Am-4900) and CM-Am.

Modified electroosmotic flow by cationic surfactant additives in capillary electrophoresis: Evaluation of electrolyte systems for anion analysis

A detailed experimental study of the variables affecting flow reversal was conducted in electrolyte systems commonly used for the determination of small anions. The electroosmotic flow mobilities of chromate (5 mM, pH 8) and 3,5-dinitrobenzoate solutions (concentration range 1.25–10 mM and pH 4–9) were determined by monitoring the migration time of pure water with indirect UV detection at 254 nm. The addition of the cationic surfactants cetyltrimethylammonium bromide, tetradecyltrimethylammonium bromide and lauryltrimethylammonium bromide, computed as fractions of the standard critical micelle concentration (std CMC), was investigated. The results suggested that flow reversal follows a single transition adsorption mechanism, in which the capillary inner surface is occupied by a layer of hemi-micelles, i.e. two dimensional aggregates formed by lateral interaction of surfactant tails. Once flow reversal is achieved, with surfactant concentration approximately above 10% std CMC, the nature of the electrolyte anion as well as the pH of the solution does not exert any significant effect on the magnitude of the electroosmotic flow. However, at this condition, the electroosmotic flow mobility varies linearly with the logarithm of the anion concentration.

Chiral separation of monoterpenes using mixtures of sulfated β-cyclodextrins and α-cyclodextrin as chiral additives in the reversed-polarity capillary electrophoresis mode

The use of mixtures of sulfated β-cyclodextrins and native α-cyclodextrin as chiral additives in capillary electrophoresis was evaluated for the chiral resolution of neutral, cyclic and bicyclic monoterpenes, including α-pinene, β-pinene, camphene and limonene. Binding properties of sulfated β-cyclodextrins towards these monoterpenes were studied. It was found that there was no enantioresolution of these terpenoids over the concentration range studied. However, the addition of α-cyclodextrin to the running electrolyte in addition to 6.5 m M sulfated β-cyclodextrins, imparted differences in the mobilities of the terpenoid enantiomers and resulted in remarkable enantiomeric separations of α-pinene ( R s = 25), β-pinene ( R s = 12), camphene ( R s = 12) and limonene ( R s = 4). The role of both α-cyclodextrin and sulfated β-cyclodextrins in these separations is discussed.

Chiral capillary electrophoresis with noncyclic oligo- and polysaccharide chiral selectors.

A number of noncyclic oligo- and polysaccharides have been used as chiral additives in capillary electrophoresis (CE). This review offers a broad survey of the types of oligo- and polysaccharides which have been investigated and also some of the conditions developed for the enantioseparation of a wide range of drugs and other racemic compounds. Details of enantioseparation mechanisms are also discussed, in addition to some of the parameters required for optimization of the enantioresolution of chiral molecules.

Nonionic surfactants for improving resolution of the priority pollutant phenols by micelle-modified capillary electrophoresis

Nonionic surfactants used as buffer additives in capillary electrophoresis improve the separation of the eleven US EPA priority pollutant phenols. A borate/phosphate buffer (pH 9.8) containing 05–2% (w/v) Tween 40 or Brij 35 surfactant gives better separation of the phenols than the same buffer with no surfactant, especially for the solution pairs 2,4-dichlorophenol/2-methyl-4,6-dinitrophenol; 2-chlorophenol/2,4-dinitrophenol; and 4-nitrophenol/2-nitrophenol. Pentachlorophenol behaves anomalously with increasing concentration of surfactant in the 0 to 0.5% range. Its net mobility is sharply reduced, and peak shape changes from the typically narrow and symmetrical CE peak to a broad, electrophoretically tailing band at a surfactant concentration near the critical micelle concentration (CMC), and then reverts to normal shape at concentrations above the CMC. Compared with CE with buffer only, the small concentrations of surfactant required to produce significant changes in selectivity have little effect on the magnitude of the electroosmotic flow or the runtime. Nonionic surfactants neither increase conductivity nor contribute to Joule heating.

Effects of alkylamines on electroosmotic flow and protein migration behaviour in capillary electrophoresis

This paper reports the use of four closely related alkylamines as running electrolyte additives in capillary electrophoresis that permit the control of electroosmotic flow and protein migration behaviour in uncoated capillaries. At pH 2.5 the direction of the electroosmotic flow was anodic with all additives and at constant ionic strength its magnitude increased with increasing alkylamine concentration. The observations are in qualitative agreement with a previous reported theoretical model that correlates the electroosmotic mobility with the charge density in the Stern region of the electric double layer, arising from the adsorption of the additive, and the charge density at the capillary wall due to dissociation of silanols.

Performance of Zwitterionic and Cationic Fluorosurfactants as Buffer Additives for Capillary Electrophoresis of Proteins

Abstract In this work, a study has been made of the performance of a zwitterionic fluorosurfactant and mixtures of a zwitterionic and a cationic fluorosurfactant, when used as buffer additives in capillary electrophoresis. Thus, it showed to be possible to change the direction of the electroosmotic flow by changing the pH of the buffer solution. Possible mechanisms for the behaviour of the electroosmotic flow at different pH and when using different surfactant combinations are suggested. High efficiency separations of some model proteins can be obtained, when a mixture of a cationic and a zwitterionic fluorosurfactant is added to the running buffer solution. By changing concentration proportions between the surfactants, a change in separation selectivity is obtained. This procedure provides an alternative way for selectivity tuning in protein separations by capillary electrophoresis.

Simultaneous enantioselective determination and quantification of dimethindene and its metabolite N-demethyl-dimethindene in human urine using cyclodextrins as chiral additives in capillary electrophoresis

Capillary electrophoresis (CE) has been used for the chiral resolution of the basic racemic drug dimethindene (Fenistil) and its metabolite N-demethyl-dimethindene. After oral administration of 4 mg dimethindene maleate the enantioselective excretion in human urine was determined by capillary electrophoresis using a 50 mM phosphate run buffer (pH 3.3) containing 30 mM hydroxypropyl-beta-cyclodextrin. The determination of very low concentrations of dimethindene and N-demethyl-dimethindene in human urine was possible using sample stacking conditions to increase the amount of analyte in the capillary with good peak forms and resolutions. The detection limit of the method was approximately 1 ng ml-1 urine for each compound.

Chiral separations of basic drugs and quantitation of bupivacaine enantiomers in serum by capillary electrophoresis with modified cyclodextrin buffers

Modified cyclodextrin derivatives were evaluated as the buffer additives in capillary electrophoresis of several recemic pharmaceutical bases. Uncoated and polyacrylamide-modified silica capillaries were compared for their effectiveness in the enantiomeric resolution and migration reproducibility of model solutes. Using cationic detergents in the mixed-micellar mode, optimized separations of the racemic drug bupivacaine are demonstrated in a spiked serum sample at the therapeutic level. Precision, linearity and sensitivity of the method appear adequate for reliable quantitation required in pharmacokinetic and clinical studies.