Enantiomeric differentiation of a wide range of pharmacologically active substances by capillary electrophoresis using modified β-cyclodextrins (original) (raw)
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As part of a comprehensive screening program on the separation of chiral drugs by capillary zone electrophoresis, we have investigated the enantio-separation of 54 drug racemates with i-cyclodextrin as a chiral solvating agent (CSA), thus complementing previous studies on 34 drug racemates. Fourteen out of the 54 analytes investigated have been separated into the enantiomers, yielding an overall success rate of 24.4% for 86 drug racemates investigated in total.
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.
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.
Chirality, 1996
The utility of negatively charged sulfated cyclodextrins (SCD) as chiral additives (CA) in capillary electrophoresis (CE) was studied in the chiral resolution of several compounds of pharmaceutical interest, including catecholamines such as norepinephrine, epinephrine, DOPA and their precursors, phenylalanine, and tyrosine. Experiments were conducted using 10 mM sodium phosphate monobasic solution and 2% SCD adjusted to pH 3.2 with phosphoric acid. Chiral recognition mechanisms were explored using structurally related analytes including basic, acidic, and neutral compounds as well as 3,5-dinitrobenzoyl phenylglycine, phenylalanine, and homophenylalanine. The advantage of the reversed electrophoretic polarity mode for the enantioresolution of these compounds is also discussed. 0 1996 Wiley-Liss, Inc.
Journal of High Resolution Chromatography, 1996
High resolution could be achieved for the enantiomers of acidic drugs, namely, sulindac, fenoprofen, ketoprofen, warfarin, and hexobarbital, in a buffer of pH 3 by the simultaneous addition of uncharged and charged b-cyclodextrin derivatives. The interaction of the analytes with the anionic sulfobutyl ether P-cyclodextrin provides the analytes with an adequate electrophoretic mobility whereas the interaction with various neutral P-cyclodextrins generates high enantioselectivity. Five neutral cyclodextrins, the native P-cyclodextrin, as well as methyl-, dimethyl-, trimethyl-and hydroxypropyl-P-cyclodextrin, were tested to enhance the enantioselectivity of the electrophoretic system. High resolution values and the shortest analysis times for the five drugs tested were achieved in a buffer made of 100 mM phosphoric acid adjusted to pH 3 with triethanolamine and containing dimethyl-or trimethyl-0-cyclodextrin in addition to sulfobutyl ether P-cyclodextrin.
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.
Chiral separation of basic drugs by capillary electrophoresis with carboxymethylcyclodextrins
Journal of Chromatography A, 2002
Capillary electrophoresis (CE) with carboxymethylated bor g-cyclodextrins was used to achieve the rapid enantiomeric separation of a set of basic drugs. The enantiomers of 12 chiral amino-containing pharmaceutical compounds belonging to various therapeutic categories were analyzed by CE using an uncoated 60 cm375 mm I.D. silica capillary. Several experimental parameters such as the nature, concentration and pH of the buffer, nature and concentration of the anionic cyclodextrin and temperature were studied in order to optimize the enantiomeric separation. The variation of the solute partition coefficient for the chiral selector, the enantioselectivity and resolution factors are used to assess the quality of the chiral separation. It is shown that the solute affinity for the chiral selector is not related to its enantioresolution factor. None of the two cyclodextrin selectors used was able to separate the whole set of basic drugs.
ELECTROPHORESIS, 2003
Four chiral basic analytes, namely methadone, fluoxetine, venlafaxine, and tramadol, were selected as model compounds for investigating their stereoselective separation with highly sulfated g-cyclodextrin (HS g-CD) by capillary electrophoresis (CE)-UV and CE-mass spectrometry (MS). At high concentration of chiral selector, the preferentially bonded enantiomer migrated faster in the anodic mode to the detector and high resolutions were obtained for all analytes. In the cathodic mode, at lower highly sulphated cyclodextrin (HS-CD) concentration, basic compounds could be detected, with the weakly bonded enantiomer migrating first (enantiomeric migration order inversion). It was also then possible, at intermediate HS-CD concentration, that only one enantiomer migrated to the detector as cation while the other enantiomer complexed with the CD was negatively charged and presented an opposite mobility. The latter never reached the detector achieving a perfect enantiomeric selectivity. Infinite chiral resolutions were thus achieved by CE-UV as well as by CE-electrospray ionisation (ESI)-MS where concentrations of HS-CD were adapted according to the negative contribution of the nebulization gas pressure of the interface.
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.
Application of Sulfated Cyclodextrins to Chiral Separations by Capillary Zone Electrophoresis
Analytical Chemistry, 1996
Mixtures of randomly substituted sulfated cyclodextrins (degree of substitution, ∼7-10) were successfully used as chiral additives for the enantioseparation of 56 compounds of pharmaceutical interest, including anesthetics, antiarrhythmics, antidepressants, anticonvulsants, antihistamines, antihypertensives, antimalarials, relaxants, and bronchodilators. The separations were accomplished at pH 3.8, with the anode at the detector end of the column. Under these conditions, in which electroosmotic flow is directed toward the injection end of the column and the electrophoretic mobility of the negatively charged cyclodextrin is toward the detector, none of the analytes reached the detector in the absence of the sulfated cyclodextrin. Most (40) of the successfully resolved enantiomers contained basic functionality and a stereogenic carbon. However, the versatility of this sulfated cyclodextrin additive was also demonstrated by the fact that three atropisomers, 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate, 1,1′-binaphthyl-2,2′-diol, and Troger's base, and several neutral analytes were also successfully enantioresolved under these conditions. The separation mechanism seems to involve inclusion complexation.