Capillary electrophoresis , enantioselective

Esteban J, de la Cruz Pellin M, Gimeno C, Barril J, Mora E, Gimenez J, Vilenova E. Detection of clinical interactions between methadone and anti-retroviral compounds using an enantioselective capillary electrophoresis for methadone analysis. Toxicol Lett 2004 151 243-9. 

Bortocan and Bonato [112] presented a capillary electrophoresis method for the enantioselective analysis of primaquine and its metabolite carboxyprimaquine. The method is used for the simultaneous determination of the drug and its metabolite, in... 

Capillary Electrophoresis with Enantioselective Supporting Electrolytes... 

This review provides an overview of the literature published to date on macrocyclic antibiotics exploited for enantioselective separations in high-performance liquid chromatography (HPLC). It was not intended as a comprehensive issue on the applications of such antibiotics in sub- and supercritical fluid chromatography (SFC), thin layer chromatography (TLC), capillary electrophoresis (CE), and capillary electrochromatography (CEC). A number of structural properties of the most important macrocyclic antibiotics applied in HPLC enantioseparations are listed in Table 2.1. 

Ward, T.J. and Oswald, T.M., Enantioselectivity in capillary electrophoresis using the macrocyclic antihiotics, J. Chromatogr. A, 792, 309, 1997. 

Jimidar, M.I., Vennekens, T., Van Ael, W., Redlich, D., De Smef M. Optimization and validation of an enantioselective method for a chiral drug with eight stereo-isomers in capillary electrophoresis. Electrophoresis 2004, 25, 2876-2884. 

Chiral separation of drng molecules and of their precursors, in the case of synthesis of enantiomerically pure drugs, is one of the important application areas of HPLC in pharmaceutical analysis. Besides HPLC, capillary electrophoresis (CE) is another technique of choice for chiral separations. Chapter 18 provides an overview of the different modes (e.g., direct and indirect ones) of obtaining a chiral separation in HPLC and CE. The direct approaches, i.e., those where the compound of interest is not derivatized prior to separation, are discussed in more detail since they are cnrrently the most frequently used techniques. These approaches require the use of the so-called chiral selectors to enable enantioselective recognition and enantiomeric separation. Many different molecnles have been nsed as chiral selectors, both in HPLC and CE. They can be classified into three different groups, based on their... 

Capillary electrophoresis offers a set of important advantages that make it a premier technique for the investigation of enantioselective effects in the affinity interactions between chiral drugs and cyclodextrins. The most important advantage of CE is the inherently high separation efficiency offered by this technique. As already known, the most important contributors to peak resolution (R) are a separation selectivity (a) and an efficiency (N). A relationship between these parameters in CE is described by the following equation (2) ... 

B. Capillary Electrophoresis Methods for Determination of Enantioselective Binding Constants Between Chiral Drugs and Cyclodextrins... 

III. APPLICATION OF CAPILLARY ELECTROPHORESIS FOR DETERMINATION OF ENANTIOSELECTIVE BINDING CONSTANTS OF CHIRAL DRUG/CYCLODEXTRIN COMPLEXES... 

Capillary electrophoresis has been applied for the enantioselective determination of the binding constants of chiral drugs with cyclodextrins for basically the following two reasons (1) optimization of chiral selector concentration and (2) understanding the fine mechanisms of enantioseparations in CE. The first group of studies have been published mainly on the early stage of chiral CE development, whereas the second goal is followed in the most recent studies, mainly by Rizzi and Kremser (10,13) and Scriba et al. 

T Ohara, A Shibukawa, T Nakagawa. Capillary electrophoresis frontal analysis for microanalysis of enantioselective protein binding of a basic drug. Anal Chem 67 3520-3525, 1995. 

Y Kuroda, A Shibukawa, T Nakagawa. The role of branching glycan of human eq-acid glycoproten in enantioselective binding to basic drugs as studied by capillary electrophoresis. Anal Biochem 268 9-14, 1999. 

NAL Mohamed, Y Kuroda, A Shibukawa, T Nakagawa, ST Elo Gizawy, HF Askal, ME El Kommos. Enantioselective binding analysis of verapamil to plasma lipoproteins by capillary electrophoresis-frontal analysis. J Chromatogr A 875 447-453, 2000. 

PK Owens, AF Fell, MW Coleman, M Kinns, JC Berridge. Use of H -NMR spectroscopy to determine the enantioselective mechanism of neutral and anionic cyclodextrins in capillary electrophoresis. J Pharm Biomed Anal 15 1603-1619, 1997. 

X Zhu, Y Ding, B Lin, A Jakob, B Koppenhoefer. Study of enantioselective interactions between chiral drugs and serum albumin by capillary electrophoresis. Electrophoresis 20 1869-1877, 1999. 

L Valtecha, J Mohammad, G Pettersson, S Hjerten. Chiral separations of j8-blockers by high-performance capillary electrophoresis based on nonimmo-bilized cellulase as enantioselective protein. J Chromatogr 638 263—267, 1993. 

DK Lloyd, S Li, P Ryan. Investigation of enantioselective ligand—protein binding and displacement interactions using capillary electrophoresis. Chirality 6 230-238, 1994. 

DK Lloyd, A Ahmed, F Pastore. A quantitative relationship between capacity factor and selector concentration in capillary electrophoresis and high-performance liquid chromatography evidence from the enantioselective resolution of benzoin using human serum albumin as chiral selector. Electrophoresis 18 958-964, 1997. 

Y Tanaka, S Terabe. Studies of enantioselectivities of avidin, avidin-biotin complex and streptavidin by affinity capillary electrophoresis. Chromatographia 49 489-495, 1999. 

H Nishi. Enantioselectivity in chiral capillary electrophoresis with polysaccharides. J Chromatogr A 792 327-347, 1997. 

Zaugg, S. Thormann, W. Enantioselective determination of drugs in body fluids by capillary electrophoresis. J. Chromatogr., A 2000, 875, 27-41. 

M. M. Rogan, K. D. Altria, and D. M. Goodall, Enantioselective separations using capillary electrophoresis, Chirality 6-.25 (1994). 

S. Fanali, Controlling enantioselectivity in chiral capillary electrophoresis with inclusion complexation, J. Chromatogr. A 792 227 (1997). 

For enantioseparation on CSPs in CEC, nonstereospecific interactions, expressed as 4>K, contribute only to the denominator as shown in Eq. (1), indicating that any nonstereospecific interaction with the stationary phase is detrimental to the chiral separation. This conclusion is identical to that obtained from most theoretical models in HPLC. However, for separation with a chiral mobile phase, (pK appears in both the numerator and denominator [Eq. (2)]. A suitable (f)K is advantageous to the improvement of enantioselectivity in this separation mode. It is interesting to compare the enantioselectivity in conventional capillary electrophoresis with that in CEC. For the chiral separation of salsolinols using /3-CyD as a chiral selector in conventional capillary electrophoresis, a plate number of 178,464 is required for a resolution of 1.5. With CEC (i.e., 4>K = 10), the required plate number is only 5976 for the same resolution [10]. For PD-CEC, the column plate number is sacrificed due to the introduction of hydrodynamic flow, but the increased selectivity markedly reduces the requirement for the column efficiency. 

In this context, there has been a considerable development of enantioselective synthetic methodologies, which have now reached a high degree of diversity and complexity. Simultaneously, this trend has created an intensive demand for stereoselective separation techniques and analytical assays for precise determination of the enantiomeric purity of chiral compounds. The development of chiral stationary phases (CSPs) or chiral selectors for gas chromatography (GC), hquid chromatography (LC) and capillary electrophoresis (CE) rapidly opened a new dimension in the area of separation technologies. 

Electrophoretic methods are widely used alternatives for the analytical determination of the enantiomeric purity of chiral compounds [194]. Due to the high elTi-ciency of capillary electrophoresis, separations can be achieved even when very low selectivities are observed. At a preparative scale, these methods are well established for the purification of proteins and cells [195] but there is very little published on enantioselective separations. Only recently, some interest in chiral preparative applications has been manifested. Separation of the enantiomers ofterbu-taline [196] and piperoxan [197] have been reported by classical gel electrophoresis using sulfated cyclodextrin as a chiral additive, while the separation of the enantiomers of methadone could be successfully achieved by using free-fluid isotachophoresis [198] and by applying a process called interval-flow electrophoresis [199]. 

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