Systematic approach to treatment of enantiomeric separations in capillary electrophoresis and liquid chromatography (original) (raw)
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Selectivity in Capillary Electrophoresis: Application to Chiral Separations with Cyclodextrins
Analytical Chemistry, 1997
In order to accurately evaluate the performances of any electrolyte medium, a clear concept of selectivity in capillary electrophoresis and related electroseparation techniques is proposed. Selectivity is defined as the ratio of the affinity factors of both analytes for a separating agent (phase, pseudophase, or complexing agent present in the background electrolyte). When in the presence of a complexing agent and if only 1:1 complexation occurs, selectivity corresponds to the ratio of the apparent binding constants and is independent of the concentration of the complexing agent. This concept is illustrated through the separations of neutral and anionic enantiomers in the presence of a cationic cyclodextrin, the mono(6-amino-6-deoxy)--cyclodextrin, as a chiral complexing agent. The values obtained for different pairs of enantiomers are discussed with regard to the functional groups that distinguish them. When the analytes have the same mobilities in free solution and in their complexed form, then the resolution equation developed in micellar electrokinetic chromatography may be applied and optimum conditions (affinity factors, chiral agent concentration) can be predicted. (52) Leliè vre, F.; Gareil, P.; Bahaddi, Y.; Galons, H.
Journal of Chromatography A, 2002
A total of 26 different cyclodextrin (CD) derivatives with different functional groups and degrees of substitution were tested against 35 basic pharmaceutical compounds in an effort to investigate their effectiveness as chiral selectors for enantiomeric separation in capillary electrophoresis (CE). Testing was performed under the same conditions using a low pH buffer (25 mM phosphate buffer at pH|2.5). Five CD derivatives, namely, highly sulfated-b-CD, highly sulfated-a-CD, hydroxypropyl-b-CD (degree of substitution|1), heptakis-(2,6-O-dimethyl)-b-CD, and heptakis(2,3,6-O-trimethyl)-b-CD were identified to be most effective for enantiomeric separations and have a wide range of enantiomeric selectivity towards the model compounds. Over 90% of the model compounds were enantiomerically resolved with the five identified CD derivatives, at a minimum resolution of 0.5. An additional 20 compounds were also tested to demonstrate the validity of the identified CD derivatives. The five CD derivatives were recommended as the starting chiral selectors in developing enantiomeric separation methods by CE.
Analytical Chemistry, 1997
Defined as the ratio of the affinity factors of the analytes for a complexing agent, the intrinsic selectivity is representative of the very nature of the complexing agent. When more than one complexing agent are present in the background electrolyte, it is possible to define several intrinsic selectivities according to whether complexing agents are considered separately or all together. A theoretical model with respect to selectivity is presented for separations that involve two complexing agents, using the concept of apparent constant for complex formation. When only independent complexation occurs (absence of mixed complexes), then the intrinsic selectivity of a complexing agent X in the presence of a complexing agent Y can be easily related to the intrinsic selectivity of each complexing agent and to complex formation constants. Dual systems of cyclodextrins (CDs), implementing the cationic mono(6-amino-6-deoxy)--cyclodextrin ( -CD-NH 2 ) and a neutral CD (trimethyl--CD (TM--CD) or dimethyl--CD (DM--CD)), were studied to illustrate this model and to offer an alternative to the separation of neutral enantiomers when -CD-NH 2 shows no or insufficient stereoselectivity. With a dual -CD-NH 2 /TM--CD system at pH 2.3, arylpropionic acid enantiomers were baseline resolved and benzoin derivatives were partially resolved. For the arylpropionic acids, -CD-NH 2 , which is not stereoselective, confers on them a nonzero mobility, while TM--CD allows the chiral recognition. A study of the respective influence of ΤM--CD and -CD-NH 2 concentrations was performed to determine the optimal conditions with respect to resolution. This theoretical approach allowed characterization of the intrinsic selectivity of neutral CDs for pairs of neutral enantiomers and therefore identification of the potential of neutral chiral agents for neutral enantiomers.
Journal of Pharmaceutical and Biomedical Analysis, 1996
Three fl-cyclodextrin derivatives--carboxymethyl-, dimethyl-and hydroxypropyl-fl-cyclodextrin--were tested as chiral selectors for the enantioseparation of seven basic drugs in free solution capillary electrophoresis, using buffers made of 100 mM phosphoric acid adjusted to pH 3.0 with triethanolamine in fused silica capillaries thermostatted at 15°C. The best results with respect to chiral resolution were obtained with carboxymethyl-fl-cyclodextrin (CMCD): the enantiomers of all compounds examined were completely resolved with this fl-cyclodextrin derivative. The influence of the CMCD concentration on the migration times, the apparent electrophoretic mobility difference and the resolution of the drug enantiomers was investigated thoroughly. Particularly impressive resolution values, up to 23.7, were obtained for several compounds in these capillary electrophoretic systems, using CMCD in the 5-15 mM concentration range.
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.
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.
Journal of Microcolumn Separations, 1998
The single isomer, fully and permanently charged heptakis-2,3-di-. methyl-6-sulfato--cyclodextrin was used to study the complexation behavior of the enantiomers of noncharged analytes in capillary electrophoresis. Separation selectivities were calculated from the measured effective mobilities and were used to determine the individual complexation constants by fitting the experimentally obtained selectivity values to the theoretically derived selectivity expression according to the charged resolving agent migration model of capillary electrophoresis. Ž. Though heptakis-2,3-dimethyl-6-sulfato--cyclodextrin complexed very weakly with the neutral analytes studied, good separation selectivities were observed. For all neutral analytes, separation selectivity decreased with increasing concentration of the charged cyclodextrin as long as the analytical concentration of the charged cyclodextrin was much greater than that of the analyte. In addition to adequate separation selectivity, good peak resolution required the simultaneous control of the magnitude of both the effective charge of the analyte and the dimensionless electroosmotic flow rate.
Enantioselective determination by capillary electrophoresis with cyclodextrins as chiral selectors
Journal of Chromatography A, 2000
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.