Use of cyclodextrins in capillary electrophoresis for the chiral resolution of some 2-arylpropionic acid non-steroidal anti-inflammatory drugs (original) (raw)
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Use of cyclodextrins in capillary electrophoresis
1993
Capillary zone electrophoresis was successfully applied to the enantiomeric resolution of racemic tramadol. Both uncoated and polyacrylamide-coated capillaries were tested for method optimization using either negatively charged or native cyclodextrins (CD) added to the background electrolyte (BGE). The resolution was strongly influenced by the CD type and concentration as well as by the pH and the concentration of the BGE. Among the CDs tested, carboxymethylated-P-cyclodextrin allowed the baseline separation of tramadol enantiomers. After the method was optimized, it was validated in a coated capillary for enantiomeric analysis of tramadol enantiomers in pharmaceutical formulation, including specificity and elution order, linearity, accuracy and precision, determination of limit of detection (LOD) and quantification (LOQ), enantiomeric purity linearity, freedom from interference, and stability of sample solutions. Precision at the target concentration was less than 2%, with an accuracy higher than 99%. Furthermore, the method was able to detect 0.3% and to quantify 1% of the minor enantiomer in the presence of the major one at the target value.
ELECTROPHORESIS, 2004
The possibility to enhance resolution to infinite value in chiral capillary electrophoresis is attained as soon as the apparent mobility of one enantiomer becomes opposite to the other. This could be achieved on the basis of the carrier ability of multiple charged chiral selectors such as highly sulfated cyclodextrin (HS-CD). With tramadol and its phase I metabolites selected as model compounds, the HS-g-CD was found to be the most appropriate chiral selector. The CD concentration was determined where one enantiomer still migrated as a cation while the other migrated in the opposite side. Besides the chiral selector concentration, secondary parameters such as buffer concentration appeared to be critical to reach infinite resolution. The latter was achieved with partial filling technique using ultrashort separation zones (a few mm). In order to better understand the interaction mechanism between the selected CD and the analytes, the classical affinity capillary electrophoresis method, although not fully satisfactory because of ionic strength variations within a series of mobility shift measurements, was applied to estimate complexation constants and complex mobilities. The results obtained point to the prevailing role of complex mobility differences in the enantioselectivity mechanism.
Use of cyclodextrins in capillary zone electrophoresis
Journal of Chromatography A, 1991
Capillary zone electrophoresis was successfully applied to the enantiomeric resolution of racemic tramadol. Both uncoated and polyacrylamide-coated capillaries were tested for method optimization using either negatively charged or native cyclodextrins (CD) added to the background electrolyte (BGE). The resolution was strongly influenced by the CD type and concentration as well as by the pH and the concentration of the BGE. Among the CDs tested, carboxymethylated-P-cyclodextrin allowed the baseline separation of tramadol enantiomers. After the method was optimized, it was validated in a coated capillary for enantiomeric analysis of tramadol enantiomers in pharmaceutical formulation, including specificity and elution order, linearity, accuracy and precision, determination of limit of detection (LOD) and quantification (LOQ), enantiomeric purity linearity, freedom from interference, and stability of sample solutions. Precision at the target concentration was less than 2%, with an accuracy higher than 99%. Furthermore, the method was able to detect 0.3% and to quantify 1% of the minor enantiomer in the presence of the major one at the target value.
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.
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.
Chromatographia, 1996
13-cyclodextrin derivatives, namely 6 A methylamino-13-CD and hepta-methylamino-J3-CD have been used as chiral selectors for the enantiomeric separation of a number of acidic and basic compounds by capillary electrophoresis employing either coated or uncoated capillaries. The effects of the CD type and concentration and the pH of the background electrolyte on the mobility and chiral resolution of the analytes have been studied. The use of monomethylamino-13-CD in a coated capillary allowed the enantiomeric resolution of phenyl lactic acid, warfarin and acenocoumarol but was not successful for tiaprofen and its 3-isomer. The heptamethyl~ amino derivative, under the same experimental conditions, was a better chiral selector than the monosubstituted CD toward the arylpropionic acids and phenyl lactic acid while the anticoagulant drugs showed poor or no chiral resolution. Inversion of migration order was obtained for phenyl lactic acid, warfarin and acenocoumarol enantiomers. The enantiomers of basic compounds of pharmaceutical interest, namely propranolol, terbutaline, ketamine, chlorpheniramine and isoproterenol were only resolved using monomethylamino-~-CD dissolved in a phosphate buffer containing tetramethylammonium ions.
Electrophoresis, 1997
Nine nonsteroidal anti-inflammatory drugs (NSAIDs) were enantioseparated by capillary electrophoresis using an anionic cyclodextrin derivative (sulfobutyl ether B-cyclodextrin or carboxymethyl-P-cyclodextrin) in combination with a neutral cyclodextrin as chiral additives to a pH 3 phosphoric acid-triethanolamine buffer. In the presence of a negatively charged cyclodextrin, the analytes were given an appropriate mobility but relatively low enantioselectivities were generally obtained when such a cyclodextrin was the only selector added to the buffer. The addition of an uncharged cyclodextrin, such as the native B-cyclodextrin or one of its derivatives (dimethyl-, trimethyl-and hydroxypropyl-fi-cyclodextrin), to this kind of buffer containing an anionic cyclodextrin, was found to give rise to considerable improvement in chiral resolution for all compounds studied. Resolution and analysis time were optimized by varying the nature and concentration of the two cyclodextrins. The best compromise was usually achieved by the simultaneous addition of sulfobutyl ether 0-cyclodextrin and trimethyl-0-cyclodextrin. Under optimum conditions, the enantiomers of all NSAIDs examined could be completely separated (most often with resolution values higher than 5) in short analysis times (generally lower than 15 min). Correspondence: Prof. J. Crommen, Laboratory of Drug Analysis, Institute of Pharmacy, University of Liege, rue Fusch, 5, B-4000 Liege, Belgium (Tel: +32-4-2322-962; Fax: +32-4-2322-937)
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.