Electrophoretic chiral separation of pharmaceutical compounds with multiple stereogenic centers in charged cyclodextrin media

Fang, Wang; Dowling, Thomas M.; Bicker, G.; Wyvratt, Jean

doi:10.1002/1615-9314(20010501)24:5<378::aid-jssc378>3.0.co;2-m

Cited by 15 publications

(2 citation statements)

References 28 publications

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“…However, the pure single enantiomer may be commercially unavailable or expensive, especially for chiral analysis of newly developed chiral drugs and multiple chiral centers drugs. As a result, the identification of enantiomeric peak was not completed in many chiral separation works. − Because enantiomers have the same mass-to-charge ratio, mass spectrometry (MS) with powerful qualitative ability was thought to be blind in chiral analysis in the past until some chiral molecules were distinguished based on different mechanisms of host–guest association, ion/molecule (equilibrium) reactions, collision-induced dissociation of diastereomeric complex, or ion mobility spectrometry . However, these methods are strictly limited to isotope labeling, suitable ligands, or specific MS that can store fragments .…”

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Identification and Quantitation of Enantiomers by Capillary Electrophoresis and Circular Dichroism Independent of Single Enantiomer Standard

et al. 2019

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Identification and quantitation of enantiomers is a critical and challenging step in the process of chiral capillary electrophoresis (CE) analysis, especially when the optically pure enantiomers are expensive or commercially unavailable. Herein, a method of CE in combination with circular dichroism (CD) spectroscopy for the identification of enantiomeric peak independent of single enantiomer standard was proposed. By comparing the theoretical CD spectrum of the single enantiomer calculated by time-dependent density functional theory (TDDFT) with the experimental CD spectrum of the enantiomeric mixture, the configuration of the dominant enantiomer in the nonracemic mixture was determined. Considering that the dominant enantiomer showed bigger peak area on the CE electrophoretogram, the enantiomeric peak was easily identified. Three kinds of enantiomers including seven chiral compounds (i.e., tryptophan, tyrosine, phenylalanine, Boc-valine, Boc-leucine, ibuprofen, and naproxen) were used to evaluate the reliability of the method. The concentration of the single enantiomer in the mixture can be further accurately quantified based on the total concentration of the mixture and the peak area ratio of a couple of enantiomers, and the accuracy was assessed by taking ibuprofen as an example. The developed CE-CD method provides an alternative tool for the analysis of nonracemic mixture with good ECD signals.

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Identification and Quantitation of Enantiomers by Capillary Electrophoresis and Circular Dichroism Independent of Single Enantiomer Standard

et al. 2019

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“…Entre os derivados carregados de CDs disponíveis comercialmente, destacam-se a β-CD carboxilada, a β-CD sulfobutiléter e a β-CD sulfatada. Essas CDs estão sendo cada vez mais citadas na literatura, em um grande número de separações quirais para compostos de diferentes classes 81,[84][85][86][87][88][89][90][91][92][93][94][95] . A separação de enantiômeros empregando os derivados de CDs depende não apenas do tipo de CD e de sua concentração, mas também de outras características como grau de substituição e posição em que os substituintes se encontram.…”

Section: Separação De Enantiômeros Por Ceunclassified

Análise enantiosseletiva de fármacos: contribuições da cromatografia líquida de alta eficiência e eletroforese capilar

Bonato¹,

Jabor²,

Gaitani³

2005

Quím. Nova

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Recebido em 2/7/04; aceito em 6/10/04; publicado na web em 17/2/05 ENANTIOSELECTIVE ANALYSIS OF DRUGS: CONTRIBUTIONS OF HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY AND CAPILLARY ELECTROPHORESIS. The demand for analytical methods suitable for accurate and reproducible determination of drug enantiomers has increased significantly in the last years. High-performance liquid chromatography (HPLC) using chiral stationary phases and capillary electrophoresis (CE) are the most important techniques used for this purpose. In this paper, the fundamental aspects of chiral separations using both techniques are presented. Some important aspects for the development of enantioselective methods, particularly for the analysis of drugs and metabolites in biological samples, are also discussed.Keywords: chiral drugs; high-performance liquid chromatography; capillary electrophoresis. INTRODUÇÃOPor razões econômicas e dificuldades de ordem prática nos processos de produção, a maioria dos fármacos quirais obtidos por vias sintéticas é comercializada como racemato, ou seja, mistura contendo quantidades iguais dos dois enantiômeros 1 . No entanto, existem inúmeros exemplos de fármacos que apresentam atividades farmacológicas estereosseletivas (propriedades farmacodinâmicas), conseqüência de interações com receptores biológi-cos, que são altamente específicas 2 . Um exemplo clássico que não pode ser esquecido é o da talidomida. Somente depois das investigações da contribuição das propriedades estereosseletivas desse fármaco, é que foi possível estabelecer que as propriedades teratogênicas da talidomida, que causaram deformidades físicas em recém nascidos cujas mães fizeram uso desse fármaco durante a gravidez, estavam relacionadas com o enantiômero (-)-(S)-3 . Infelizmente, em estudos posteriores foi constatada a inversão de configuração não apenas in vitro mas também in vivo da talidomida 4,5 , evidenciando que se o enantiômero (+)-(R)-puro tivesse sido administrado, teria sido parcialmente convertido no isômero responsável pelo efeito teratogênico. Exemplos menos drásticos que esse são bastante comuns, nos quais as diferenças existentes entre os dois enantiômeros podem ser qualitativas ou quantitativas, sendo que, nesse último caso, o enantiômero mais ativo é chamado de eutômero enquanto que ao outro dá-se o nome de distômero 6 . Estudos têm mostrado que β-bloqueadores, propranolol é um exemplo, se ligam estereosseletivamente a receptores β-adrenérgicos e que os enantiômeros (-)-são os principais responsáveis pela atividade β-bloqueadora dessa classe de fármacos 7 . Adicionalmente, quando um fármaco quiral é administrado como racemato, os dois enantiômeros podem apresentar os processos de absorção, distribuição, metabolização e excreção (disposição cinética) de forma estereosseletiva [8][9][10][11] . Desses processos, a estereosseletividade é mais significativa no metabolismo, devido ao envolvimento do sistema enzimático. Dentre os inúmeros exemplos, pode-se destacar o verapamil; o enantiômero ativo (-)-(S) é preferencialmente metabolizado ...

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Chiral separation of the β₂‐sympathomimetic fenoterol by HPLC and capillary zone electrophoresis for pharmacokinetic studies

Ullrich

Wesenberg

Bleuel

et al. 2010

Biomedical Chromatography

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The development of methods for the separation of the enantiomers of fenoterol by chiral HPLC and capillary zone electrophoresis (CZE) is described. For the HPLC separation precolumn fluorescence derivatization with naphthyl isocyanate was applied. The resulting urea derivatives were resolved on a cellulose tris(3,5-dimethylphenylcarbamate)-coated silica gel column employing a column switching procedure. Detection was carried out fluorimetrically with a detection limit in the low ng/mL range. The method was adapted to the determination of fenoterol enantiomers in rat heart perfusates using liquid-liquid extraction. As an alternative a CE method was used for the direct separation of fenoterol enantiomers comparing different cyclodextrin derivatives as chiral selectors.

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Electrophoretic chiral separation of pharmaceutical compounds with multiple stereogenic centers in charged cyclodextrin media

Cited by 15 publications

References 28 publications

Identification and Quantitation of Enantiomers by Capillary Electrophoresis and Circular Dichroism Independent of Single Enantiomer Standard

Identification and Quantitation of Enantiomers by Capillary Electrophoresis and Circular Dichroism Independent of Single Enantiomer Standard

Análise enantiosseletiva de fármacos: contribuições da cromatografia líquida de alta eficiência e eletroforese capilar

Chiral separation of the β₂‐sympathomimetic fenoterol by HPLC and capillary zone electrophoresis for pharmacokinetic studies

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Electrophoretic chiral separation of pharmaceutical compounds with multiple stereogenic centers in charged cyclodextrin media

Cited by 15 publications

References 28 publications

Identification and Quantitation of Enantiomers by Capillary Electrophoresis and Circular Dichroism Independent of Single Enantiomer Standard

Identification and Quantitation of Enantiomers by Capillary Electrophoresis and Circular Dichroism Independent of Single Enantiomer Standard

Análise enantiosseletiva de fármacos: contribuições da cromatografia líquida de alta eficiência e eletroforese capilar

Chiral separation of the β2‐sympathomimetic fenoterol by HPLC and capillary zone electrophoresis for pharmacokinetic studies

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Chiral separation of the β₂‐sympathomimetic fenoterol by HPLC and capillary zone electrophoresis for pharmacokinetic studies