Rapid chiral separation methods development by cyclodextrin-mediated capillary electrophoresis for acidic and basic compounds (original) (raw)
Related papers
Journal of Pharmaceutical and Biomedical Analysis, 1999
A simple, systematic method was developed for rapidly screening potential capillary electrophoresis (CE) separation conditions for small, amine-containing enantiomers. During method development, 39 pairs of enantiomers were investigated and partial or complete separation was achieved in every case. Baseline resolution was achieved by these initial screening conditions in over half of the cases. The screening strategy uses a bare fused silica capillary and a pH 2.5 amine-modified phosphate buffer containing one of the selected cyclodextrins (CD): dimethyl-b-CD, hydroxypropyl-b-CD, hydroxypropyl-a-CD, hydroxypropyl-g-CD and sulfated-b-CD. An additional set of compounds have been screened by this approach to demonstrate the validity of the method. The paper outlines the experimental work carried out to develop the screen and describes how one might implement it for a new compound.
Analytica Chimica Acta, 2006
The chiral resolving ability of a novel single-isomer cationic -cyclodextrin (CD), mono-6 A-propylammonium-6 A-deoxy--cyclodextrin chloride (PrAMCD), as a chiral selector in capillary electrophoresis (CE) is reported in this work for the enantioseparation of hydroxy, carboxylic acids and amphoteric analytes. The effect of chiral selector concentration on the resolution was studied. Good resolutions were achieved for hydroxy acids. Optimum resolutions were obtained even at 3.5 mM CD concentration for carboxylic acids. The electrophoretic method showed good linearity and reproducibility in terms of migration times and peak areas, which should make it suitable for routine analysis. In addition, baseline chiral separation of a six-acid mixture was achieved within 20 min. PrAMCD proved to be an effective chiral selector for acidic analytes.
Separation of chiral compounds by capillary electrophoresis
Electrophoresis, 1998
This review presents the different chiral selectors used in capillary electrophoresis (CE) for the separation of enantiomers . The use of charged cyclodextrins. crown ethers. polysaccharides. proteins. natural and synthetic micelles. macrocyclic antibiotics and ergot alkaloids is discussed in detail . Neutral native and derivatized cyclodextrins are not treated because several review articles have already been published on this topic . Recent developments like the application of two chiral selectors in the same background electrolyte are highlighted .
Capillary Electrophoresis: an attractive technique for chiral separations
Capillary Electrophoresis (CE) separates compounds that differ in charge to hydrodynamic size ratio and is an excellent technique for the analysis of polar compounds. The technique is particularly applicable to chiral separations. Chiral CE separation is achieved by adding a chiral selector to the so called background electrolyte. The enantiomers then form fast, reversible equilibria with the selector. In this paper a simple method development strategy for basic, acidic and neutral compounds is presented and illustrated with examples and common pitfalls. Some important good working practices (background electrolyte buffer recipes, temperature, corrected peak area, injection, polyimide coating removal from capillary ends) are highlighted, so that a good chiral separation can be developed into a robust analytical method.
Chirality, 2003
This review focuses on the emerging role of sulfated cyclodextrins in the capillary electrophoretic (CE) separation of chiral analytes. Since being introduced as enantioselective agents for CE in 1995, these anionic additives have continued to demonstrate remarkable application universality. The broad spectrum of chiral compounds successfully separated using this approach includes acidic, basic, neutral, and zwitterionic species. This impressive array of analyte structures is derived from a growing diversity of compound classes including pharmaceuticals, plant extracts, biomarkers, herbicides, alkaloids, fungicides, and metal ions. Moreover, literature reports highlight the minimal optimization required to achieve a successful separation. Based on these findings, sulfated cyclodextrins appear to be well suited for the development of a more universal, comprehensive separation strategy for chiral compounds. This review explores this proposition by beginning with the structure and migration properties of sulfated cyclodextrins, using applications to highlight the separating power of this technique and ending with a pragmatic, comprehensive separation strategy. Chirality 15:709–723, 2003. © 2003 Wiley-Liss, Inc.
Journal of Chromatography A, 1997
Enantioseparation in capillary electrophoresis using 2-O-(2-hydroxybutyl)-â-CD as a chiral selector The resolving ability of 2-O-(2-hydroxybutyl)-b-CD (HB-b-CD) with different degrees of substitution (DS = 2.9 and 4.0) as a chiral selector in CZE is reported in this work. Fourteen chiral drugs belonging to different classes of compounds of pharmaceutical interest such as b-agonists, antifungal agents, ageneric agents, etc., were resolved. The effects of the DS of HB-b-CD on separations were also investigated. The chiral resolution (R s) was strongly influenced by the concentrations of the CD derivative, the BGE, and the pH of the BGE. Under the conditions of 50 mmol/L Tris-phosphate buffer at pH 2.5 containing 5 mmol/L HB-b-CD, all 14 analytes were separated. The very low concentration necessary to obtain separation was particularly impressive. The DS had a significant effect on the resolution of the chiral drugs and the ionic strength of the separation media; hence, the use of a well-characterized CD derivative is crucial.
Practical aspects in chiral separation of pharmaceuticals by capillary electrophoresis
Journal of Chromatography A, 1994
In recent years, there has been considerable activity in the separation and characterization of optically active molecules. In this paper we report a new, improved and automated electrophoretic method for the separation of enantiomers in the form of high-performance capillary gel etectrophoresis using hydroxypropyl-P-cyclodextrin as a chiral selector. Rapid, efficient separation of naproxen enantiomers is shown with very low detection limits and excellent. detection linearity. The intra-and inter-day as well as intra-and inter-column migration time reproducibility was less than 2% R.S.D. Trace level enantiomeric contamination determination is also shown.
Chiral separation of basic drugs by capillary electrophoresis with carboxymethylcyclodextrins
Journal of Chromatography A, 2002
Capillary electrophoresis (CE) with carboxymethylated bor g-cyclodextrins was used to achieve the rapid enantiomeric separation of a set of basic drugs. The enantiomers of 12 chiral amino-containing pharmaceutical compounds belonging to various therapeutic categories were analyzed by CE using an uncoated 60 cm375 mm I.D. silica capillary. Several experimental parameters such as the nature, concentration and pH of the buffer, nature and concentration of the anionic cyclodextrin and temperature were studied in order to optimize the enantiomeric separation. The variation of the solute partition coefficient for the chiral selector, the enantioselectivity and resolution factors are used to assess the quality of the chiral separation. It is shown that the solute affinity for the chiral selector is not related to its enantioresolution factor. None of the two cyclodextrin selectors used was able to separate the whole set of basic drugs.