Chiral capillary electrophoresis: Facts and fiction on the reproducibility of resolution with randomly substituted cyclodextrins

Schmitt, Ulrich; Ertan, Mevlüt; Holzgrabe, Ulrike

doi:10.1002/elps.200405932

Cited by 38 publications

(29 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, when it comes to the quantification of the ratio of two isomers or the determination of the enantiomeric excess [36,37], a validation of the method has to be performed. In this case, care must be taken if randomly substituted CD derivatives were employed [38]. As has been demonstrated by the intercompany crossvalidation exercise on clenbuterol [7], CD-modified CE has a much higher separation power and robustness than chiral HPLC and should be therefore used without any reservation.…”

Section: Chiral Analysismentioning

confidence: 98%

Why not using capillary electrophoresis in drug analysis?

et al. 2006

Self Cite

View full text Add to dashboard Cite

CE and related methods are well-established techniques in the analysis of biomolecules, such as DNA and proteins. Even though CE is a rather good alternative to HPLC for the evaluation of the impurity profile and the enantiomeric purity of a drug, it is rarely applied. This might be due to the reservation of national licensing authorities and the pharmacopoeia commissions for several reasons. In this review containing some experimental data we report on several drug examples which demonstrate the superiority of CE over HPLC in special cases, i.e., in the analysis of antibiotics, amino acids and peptides, and the determination of enantiomeric purity. However, in order to make the CE techniques more suitable for pharmacopoeial purposes the general methods describing separation methods have to be complemented with the adjustment of the electrophoretic conditions being necessary to satisfy the system suitability criteria without fundamentally modifying the methods. Taken together CE should be more often applied in drug quality control.

show abstract

Section: Chiral Analysismentioning

confidence: 98%

Why not using capillary electrophoresis in drug analysis?

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…Characterization of these CDs indicated relatively good homogeneity in terms of degree of sulfation. Elemental analysis of the highly S-a-CD, highly S-b-CD, and highly S-g-CD showed that the average sulfate contents were 11, 12, and 13 per CD molecule, respectively [22], even if heterogeneity in terms of position of substitution has been proved for similar substituted CDs [23]. The molar concentration unit is used to permit the comparison of the different selectors used and the calculation of apparent and averaged binding constants.…”

Section: Chemicalsmentioning

confidence: 99%

Enantioseparation of chiralN-imidazole derivatives by electrokinetic chromatography using highly sulfated cyclodextrins: Mechanism of enantioselective recognition

et al. 2005

View full text Add to dashboard Cite

Baseline separation of ten new substituted [1-(imidazo-1-yl)-1-phenylmethyl)] benzothiazolinone and benzoxazolinone derivatives, with one chiral center, was achieved by CD-EKC using highly sulfated CDs (alpha, beta, gamma highly S-CDs) as chiral selectors. The influence of the type and concentration of the chiral selectors on the enantioseparations was investigated. The highly S-CDs exhibit a very high enantioselectivity power since they allow excellent enantiomeric resolutions compared to those obtained with the neutral CDs. The enantiomers were resolved with analysis times inferior to 2.5 min and resolution factors R(s) of 3.73, 3.90, 1.40, and 4.35 for compounds 1, 2, 3, and 5, respectively, using 25 mM phosphate buffer at pH 2.5 containing either highly S-alpha-CD, highly S-beta-CD, and highly S-gamma-CD (3 or 4% w/v) at 298 K, with an applied field of 0.30 kV/cm. The determination of the enantiomer migration order for the various analytes and the study of the analyte structure-enantioseparation relationships display the high contribution of the interactions between the analytes phenyl ring and the CDs to the enantiorecognition process. The thermodynamic study of the analyte-CD affinities permits us to improve our knowledge about the enantioseparation mechanism.

show abstract

“…Inclusion within the CD cavity is responsible for chiral discrimination [20]; CD varieties that are neutral (native or derivatized), positively charged, and negatively charged are commercially available. More recently, the trend has been to create single-isomer derivatized CDs in an attempt to reduce batch-to-batch variability and improve reproducibility [21]. Other chiral selectors include [5,22]: proteins [23,24], crown ethers [25], oligosaccharides, polysaccharides, macrocyclic antibiotics [26], and surfactant aggregates [27,28] (micelles (monomeric [29,30] and polymeric [31][32][33][34]), vesicles [35,36], and microemulsions (vide infra)).…”

Section: Introductionmentioning

confidence: 99%

Two‐chiral component microemulsion EKC – chiral surfactant and chiral oil. Part 2: Diethyl tartrate

Kahle

Foley

2007

Electrophoresis

View full text Add to dashboard Cite

In this second study on dual-chirality microemulsions containing a chiral surfactant and a chiral oil, a less hydrophobic and lower interfacial tension chiral oil, diethyl tartrate, is employed (Part 1, Foley, J. P. et al.., Electrophoresis, DOI: 10.1002/elps.200600551). Six stereochemical combinations of dodecoxycarbonylvaline (DDCV: R, S, or racemic, 2.00% w/v), racemic 2-hexanol (1.65% v/v), and diethyl tartrate (D, L, or racemic, 0.88% v/v) were examined as pseudostationary phases (PSPs) for the enantioseparation of six chiral pharmaceutical compounds: pseudoephedrine, ephedrine, N-methyl ephedrine, metoprolol, synephrine, and atenolol. Average efficiencies increased with the addition of a chiral oil to R-DDCV PSP formulations. Modest improvements in resolution and enantioselectivity (alpha(enant)) were achieved with two-chiral-component systems over the one-chiral-component microemulsion. Slight enantioselective synergies were confirmed using a thermodynamic model. Results obtained in this study are compared to those obtained in Part 1 as well as those obtained with chiral MEEKC using an achiral, low-interfacial-tension oil (ethyl acetate). Dual-chirality microemulsions with the more hydrophobic oil dibutyl tartrate yielded, relative to diethyl tartrate, higher efficiencies (100,000-134,000 vs. 80,800-94,300), but lower resolution (1.64-1.91 vs. 2.08-2.21) due to lower enantioselectivities (1.060-1.067 vs. 1.078-1.081). Atenolol enantiomers could not be separated with the dibutyl tartrate-based microemulsions but were partially resolved using diethyl tartrate microemulsions. A comparable single-chirality microemulsion based on the achiral oil ethyl acetate yielded, relative to diethyl tartrate, lower efficiency (78 300 vs. 91 600), higher resolution (1.99 vs. 1.83), and similar enantioselectivities.

show abstract

Chiral capillary electrophoresis: Facts and fiction on the reproducibility of resolution with randomly substituted cyclodextrins

Cited by 38 publications

References 29 publications

Why not using capillary electrophoresis in drug analysis?

Why not using capillary electrophoresis in drug analysis?

Enantioseparation of chiralN-imidazole derivatives by electrokinetic chromatography using highly sulfated cyclodextrins: Mechanism of enantioselective recognition

Two‐chiral component microemulsion EKC – chiral surfactant and chiral oil. Part 2: Diethyl tartrate

Contact Info

Product

Resources

About