Salvatore Fanali

Enantioselective determination by capillary electrophoresis with cyclodextrins as chiral selectors.

This review surveys the separation of enantiomers by capillary electrophoresis using cyclodextrins as chiral selector. Cyclodextrins or their derivatives have been widely employed for the direct chiral resolution of a wide number of enantiomers, mainly of pharmaceutical interest, selected examples are reported in the tables. For method optimisation, several parameters influencing the enantioresolution, e.g., cyclodextrin type and concentration, buffer pH and composition, presence of organic solvents or complexing additives in the buffer were considered and discussed. Finally, selected applications to real samples such as pharmaceutical formulations, biological and medical samples are also discussed.

Identification of chiral drug isomers by capillary electrophoresis

Separation of optical isomers of compounds of pharmaceutical interest by capillary electrophoretic techniques is reviewed. The direct and indirect separation method, as well as the main resolution mechanisms and the parameters influencing the stereoselectivity are discussed considering capillary zone electrophoresis, micellar electrokinetic chromatography, isotachophoresis and electrochromatography. Several chiral selectors have been successfully used in CE for chiral separation, including cyclodextrins and their derivatives, modified crown-ethers, proteins, antibiotics, linear saccharides and chiral surfactants. Only applications in the pharmaceutical field with the most important experimental conditions are summarised in the Tables reported in this paper. The chiral analyses of drugs in real samples like biological fluids or pharmaceutical formulations are also reported.

Use of cyclodextrins in capillary zone electrophoresis : Resolution of terbutaline and propranolol enantiomers

Abstract Terbutaline and propranolol were resolved using capillary zone electrophoresis. The effect of the type and the amount of cyclodextrins added to the background electrolyte on the migration time and the resolution of their enantiomers was studied. Good resolution of the racemic terbutaline was obtained using phosphate buffer at pH 2.5 containing either 5 m M heptakis(2,6-di-O-methyl)-β-cyclodextrin or 15 m M β-cyclodextrin. The background electrolyte, 50 m M phosphate buffer (pH—2.5) − 4 M urea − 40 m M β-cyclodextrin in 30% (v/v) methanol, on the other hand, gave the best resolution of propranolol enantiomers.

Indirect photometric detection in capillary zone electrophoresis

Abstract An indirect photometric detection method is described which is based on the use of an absorbing co-ion as the principal component of the background electrolyte. The zones of non-absorbing ionic species are revealed by changes in light absorption due to charge displacement of the absorbing co-ion. Theoretical considerations are given for selecting a suitable absorbing co-ion to achieve a high sensitivity of detection. The role of electromigration dispersion is illustrated by experiments and the effects of the differences in the effective mobilities of sample ions and that of the absorbing co-ion are discussed. The highest sensitivity can be achieved for sample ions having an effective mobility close to the mobility of the absorbing co-ion. In such a case, the concentration of the sample component in its migrating zone can be high while electromigration dispersion is still negligible. The useful dynamic range of the detection is then limited by the linearity and noise of the detector, the former parameter being given mostly by the shape of the on-column detection cell. The best sensitivities can be obtained in low-concentration background electrolytes containing a co-ion with high absorption at a given detection wavelength. It is shown that indirect photometric detection can be useful for detecting substances that have no optical absorption in the UV and/or visible region, provided that the composition of the background electrolyte is selected correctly.

Controlling enantioselectivity in chiral capillary electrophoresis with inclusion–complexation

The separation of chiral compounds is of key importance in different fields of application, e.g., pharmaceutical, industrial, forensic, biological, clinical etc. Capillary electrophoresis (CE) is a powerful analytical method applied in chiral analysis and inclusion-complexation is one of the most frequently used mechanism to improve the selectivity of the enantiomeric separation. Cyclodextrins and their derivatives or modified crown-ethers have been successfully applied in CE for the enantiomeric separation of a wide number of analytes. This review surveys the separation of enantiomers by CE when chiral selectors, forming inclusion-complexation, are used. The control of enantioselectivity can be done carefully by considering several experimental parameters such as chiral selector type and concentration, pH, ionic strength and concentration of the background electrolyte, electroosmotic flow, organic modifier etc. The review presents a list of the latest separation of enantiomers by CE where inclusion-complexation plays a key role in the stereoselective separation mechanism.

Enantioseparations by capillary electrochromatography.

The review summarizes recent developments in enantioseparations by capillary electrochromatography (CEC). Selected fundamental aspects of CEC are discussed in order to stress those features which may allow the success of this technique in the competitive field of enantioseparations. In addition, the comparative characteristics of the different modes of chiral CEC and the stationary phases are presented. The effects of the characteristics of the stationary and liquid phases and operational conditions on the separation results are discussed. Finally, some future trends are briefly addressed.

Use of negatively charged sulfobutyl ether-β-cyclodextrin for enantiomeric separation by capillary electrophoresis

Abstract A newly modified charged β-cyclodextrin (sulfobutyl ether-β-cyclodextrin) was investigated as a chiral selector in capillary electrophoresis in a study of the enantiomeric separation of a variety of underivatized anionic and cationic compounds of pharmaceutical interest and uncharged phenyl alcohols and dansyl-amino acids. Owing to the presence of four sulfonic groups, the chiral selector is negatively charged at all pH values used (2.5–9) and the complexation caused an increase in migration time for each compound studied. At a relatively low pH (2.5) the chiral selector could only be used at low concentration (0.1-0.5 mg/ml) for basic compounds, whereas at higher pH (6–9) the modified cyclodextrin in the concentration range 0–20 mg/ml was used. The concentration of the chiral selector, the distance from the aromatic group of the asymmetric centre of the analytes and the chemical composition and pH of the background electrolyte influenced the complexation, selectivity and resolution. Good enantiomeric separation was obtained for terbutaline at all pH values studied, whereas for other racemic compounds, warfarin, acenocoumarol, promethazine, bupivacaine and some dansyl-amino acids and phenyl alcohols, the pH range 6–9 was effective for optimizing the chiral resolution. Non-polar substituent groups on the asymmetric carbon of the analytes seem to enhance the complexation and the stereoselectivity.

Chiral analysis by capillary electrophoresis using antibiotics as chiral selector.

The separation of chiral compounds by capillary electrophoresis (CE) is a very interesting field of research in different areas such as pharmaceutical, environmental, agricultural analysis etc. The separation of two enantiomers can be achieved in CE using a chiral environment interacting with the two analytes on forming diastereoisomers with different stability constants and thus different mobilities. A wide number of chiral selectors have been employed in CE and among them glycopeptide antibiotics exhibited excellent enantioselective properties towards a wide number of racemic compounds. Vancomycin, ristocetin A, rifamycins, teicoplanin, kanamycin, streptomycin, fradiomycin, and two vancomycin analogues, added to the background electrolyte (BGE), are the antibiotics studied by CE running the separation in untreated and/or coated fused-silica capillary. Due to adsorption and absorption phenomena, some drawbacks can be expected when using bare fused-silica capillary, e.g., changes of electroosmotic flow (EOF), broaden peaks, reduced efficiency and low sensitivity. Coated capillary and counter current mode can be the solution to overcome the above mentioned problems. This review surveys the separation of enantiomers by CE when macrocyclic antibiotics are used as chiral selector. The enantioselectivity can be easily controlled modifying several parameters such as antibiotic type and concentration, pH, ionic strength and concentration of the background electrolyte, organic modifier etc. The paper also presents a list of the latest chiral separations achieved by CE where antibiotics were used as chiral selector.

Chiral separations by CE employing CDs.

This paper summarizes the history of chiral separations done by using electromigration methods with CDs. Several enantioresolution mechanisms and a wide number of chiral selectors have been applied to the separation of optical isomers by CE. Among them inclusion‐complexation with CDs or their derivatives played a very important role in CE. Since the beginning our group was involved in studying method optimization for enantiomer resolution by using these chiral selectors. One of our publications was the basis for further development in the field, at least for us. New chiral selectors, development of theory, new methodological approaches and a wide number of practical applications are the main results achieved in the last almost 25 years using CE as an enantioseparative technique.

Use of cyclodextrins in capillary electrophoresis for the chiral resolution of some 2-arylpropionic acid non-steroidal anti-inflammatory drugs

Abstract The enantiomeric separation of racemic compounds of some 2-arylpropionic acid non-steroidal anti-inflammatory drugs (profens), namely fenoprofen, ibuprofen, flurbiprofen, suprofen, ketoprofen and indoprofen, was performed by capillary zone electrophoresis. The separation was obtained by supporting the background electrolyte with derivatized β-cyclodextrins. The type and concentration of cyclodextrin used and the background electrolyte composition (pH and amount of methanol) influenced the complexation and the chiral resolution. All the modified β-cyclodextrins used (heptakis-2,6-di-O-methyl-β-, heptakis-2,3,6-tri-O-methyl- and 6 A -methylamino-β-cyclodextrin) showed good complexing effects with the profens tested. Tri-O-methyl-β-cyclodextrin proved to be the best stereoselective additive because it allowed the enantiomeric resolution of all the profens studied whereas the dimethylated and methylamino-β-cyclodextrin were able to separate only some of them.