Bernhard Koppenhoefer

Separation of enatiomers of drugs by capillary electrophoresis III. β-cyclodextrin as chiral solvating agent

Enantiomer separation by capillary zone electrophoresis was studied for a set of 34 chiral drugs. Keeping the concentration of beta-cyclodextrin as a chiral solvating agent as constant as possible led to the separation of seven enantiomeric pairs. Carvedilol, Tetryzoline, Tropicamide and Zopiclone gave a baseline separation, Chlorphenamine, Ketamine, and Orciprenaline a partial separation. Statistical analysis revealed that the best separation factors were observed for a medium degree of interaction with the cyclodextrin. A theory explaining this effect provides a helpful guideline for further optimization.

Direct resolution of enantiomers of 2- and 3-hydroxy acid alkyl esters by fused-silica capillary gas chromatography

Abstract The gas chromatographic resolution of enantiomers of eighteen hydroxy acids as their alkyl esters on the optically active stationary phase Chirasil-Val is described. The problem of peak tailing due to the free hydroxy group is overcome by the application of fused-silica capillary columns. Five different alcohol components of the esters were examined, the best overall results being obtained with 3-pentanol. As a rule, the l -enantiomers of 2-hydroxy acid esters are eluted first from the stationary phase containing l -valine, whereas with the 3-hydroxybutanoic acid ester the order of elution is reversed. The separation factors are closely related to structural features.

Study of enantioselective interactions between chiral drugs and serum albumin by capillary electrophoresis

The separation of the enantiomers of three basic drugs, i.e., ofloxacin, propranolol and verapamil, was achieved by affinity capillary electrophoresis (ACE), with human serum albumin (HSA) and bovine serum albumin (BSA) as chiral selectors in phosphate buffer at pH 7.4. Ofloxacin was only separated in the presence of BSA, and verapamil only with HSA, while propranolol was separated with either HSA or BSA. The effects of protein concentration and column wall adsorption on the degree of separation were investigated. Two displacers, ketoprofen and warfarin, respectively, when added to the protein containing buffer, both showed significant effects on the separation behavior. From these data it was argued that verapamil may bind to HSA at both locations known, the warfarin binding site (I) and the ketoprofen binding site (II). While with BSA, binding of ofloxacin may also occur at site I, the preferential binding site for propanolol remains controversial. A drug‐drug interaction between propranolol and ketoprofen due to opposite charges was concluded from the increase in migration time in BSA solution. The unbound concentration of verapamil enantiomers in solution in the presence of HSA, as estimated from CD‐modified capillary zone electrophoresis, was triggered not only by the HSA concentration but also by the coadditive concentration.

Separation of enantiomers of drugs by capillary electrophoresis I. γ-cyclodextrin as chiral solvating agent

Abstract Enantiomer separation was studied for a set of 57 chiral drugs. With γ-cyclodextrin as chiral solvating agent in capillary zone electrophoresis, seven enantiomeric pairs could be separated without recoursing to an optimization procedure. Possible interaction mechanisms between selector and selectand molecules are briefly discussed.

Separation of enantiomers of drugs by capillary electrophoresis. V. Hydroxypropyl-α-cyclodextrin as chiral solvating agent

In an extended chiral drug screening program, enantioseparation of 86 racemic drugs was tested with hydroxypropyl-alpha-cyclodextrin as chiral solvating agent (CSA). A total of 34 drugs out of 86 could be resolved in this straightforward approach. The number of experiments performed under identical conditions allows a correlation of the separation factors alpha(m) with the interaction strengths Rm. As shown for a subset of 23 drugs, the concentration of the CSA is a crucial parameter for further optimization.

Enantiomeric Resolution of Some Nonsteroidal Antiinflammatory and Anticoagulant Drugs Using β-Cyclodextrins by Capillary Electrophoresis

beta-cyclodextrin (CD) and its derivatives HP-beta-CD, DM-beta-CD, and TM-beta-CD have been employed as chiral selectors for the separation of three nonsteroidal antiinflammatory drugs (NSAIDs) and anticoagulant at relatively low concentration (8-15 mM) by capillary zone electrophoresis (CZE). In this study, baseline separation was achieved for ibuprofen, ketoprofen, naproxen, and warfarin. It was found that the addition of 0.1% hydroxypropyl methyl cellulose (HPMC) was effective for separation. Under these conditions, the S-(+) enantiomer eluted before R-(-) in terms of ibuprofen; the calculated energy values obtained from the molecular modeling correlated well with the elution order. An equation for calculating the pK(a) values by capillary electrophoresis was introduced, and the pK(a) values of the four chiral drugs at 25 degrees C were obtained based on the equation. The value pK(a) + 0.5 is proposed to be the suitable pH of the background electrolyte for the separation of chiral compounds containing a carboxylic group. Chirality 11:56-62, 1999

Separation of enantiomers of drugs by capillary electrophoresis, Part 6. Hydroxypropyl-β-cyclodextrin as chiral solvating agent

In an extended chiral drug screening program, enantioseparation of 86 racemic drugs was tested with hydroxypropyl-gamma-cyclodextrin as chiral solvating agent (CSA). A total of 30 drugs out of 86 could be resolved in this straightforward approach. The number of experiments performed under identical conditions allows a statistical treatment of the data. The enantioseparation of the analytes is correlated with their interaction strength with the CSA. Hence, the concentration of the CSA is a crucial parameter for optimization of the enantioseparation, as shown by a subset of 23 examples.

Separation of drug enantiomers by capillary electrophoresis: α-cyclodextrin as chiral solvating agent

SummaryEnantiomer separation by capillary zone electrophoresis was studied for a set of 59 chiral drugs. With α-cyclodextrin as chiral solvating agent, six enantiomeric pairs could be resolved. Baseline separation was achieved for clidinium bromide, oxomemazine and tetryzoline, whereas ketamine, orphenadrine, tropicamide and others require further optimization. Aliphatic and monocyclic compounds prevail among compounds recognized by α-cyclodextrin. Statistical analysis reveals that a medium degree of migration retardation offers the best chance for successful separation.

Chiral Recognition in Gas Chromatographic Analysis of Enantiomers on Chiral Polysiloxanes

Summary The present article is a critical review on enantiomer resolution by gas chromatography on chiral amides, with emphasis on the thermostable polysiloxane Chirasil-Val. Thermodynamic studies demonstrate the significance of hydrogen bonding. Chiral recognition factors can describe chiral recognition quantitatively. Further insight is given by considering the conformations of both solute and solvent.

Separation of Enantiomers of Drugs by Capillary Electrophoresis with Permethyl‐gamma‐Cyclodextrin as Chiral Solvating Agent

High-throughput screening is a promising new approach in analytical chemistry. within the framework of an extended screening program (the german-chinese drug screening program), the enantioseparation of 86 drugs was investigated by capillary zone electrophoresis in the presence of the chiral solvating agent (csa) octakis-(2,3,6-tri-o-methyl)-gamma-cyclodextrin (tm-gamma-cd). by this means, 15 drugs could be separated into enantiomeric pairs. approximate measures for the degree of interaction (migration retardation factor, r-m) and for the degree of enantiomer recognition (migration separation factors, alpha(m)) revealed intriguing patterns that were compared with those found for native gamma-cyclodextrin (gamma-cd). although there is a distinct influence of the analyte structure on the electrophoretic data, interpretation remains difficult. most remarkably, permethylation of gamma-cd leads neither to a higher affinity nor to better chiral recognition, in contrast to the findings with alpha-cd.