Enantioselective analysis of ibuprofen in human plasma by anionic cyclodextrin-modified electrokinetic chromatography

Abstract

This paper reports the development of a rapid method for the enantioselective analysis of the nonsteroidal anti-inflammatory drug ibuprofen in human plasma by capillary electrophoresis employing the anionic cyclodextrin-modified electrokinetic chromatography mode. Sample cleanup was carried out by acidification with HCl followed by liquid-liquid extraction with hexane:isopropanol (99:1 v/v). The complete enantioselective analysis was performed within 10 min, using 100 mmol L(-1) phosphoric acid/triethanolamine buffer, pH 2.6, containing 2.0% w/v sulfated beta-cyclodextrin as chiral selector; fenoprofen, another nonsteroidal anti-inflammatory drug, was used as internal standard. The calibration curves were linear over the concentration range of 0.25-125.0 microg mL(-1) for each enantiomer of ibuprofen. The mean recoveries for ibuprofen enantiomers were up to 85%. The enantiomers studied could be quantified at three different concentrations (0.5, 5.0 and 50.0 microg mL(-1)) with a coefficient of variation and relative error not higher than 15%. The quantitation limit was 0.2 microg mL(-1) for (+)-(S)- and (-)-(R)-ibuprofen using 1 mL of human plasma. The plasma endogenous compounds and other drugs did not interfere with the present assay. The analysis of real plasma samples obtained from a healthy volunteer after administration of 600 mg of racemic ibuprofen showed a maximum plasma level of 29.6 and 39.9 microg mL(-1) of (-)-(R)- and (+)-(S)-ibuprofen, respectively, and the area under plasma concentration-time curve AUC(0-infinity) (+)-(S)/AUC(0-infinity) (-)-(R) ratio was 1.87.

Sensitive chiral analysis by capillary electrophoresis

“…Offline LLE has been employed for the extraction and preconcentration of drugs in biological samples and pollutants in culture media. The detection up to 10 28 -10 26 M of drugs (such as disopyramide, praziquantel, fluoxetine, ibuprofen, ketoprofen, tramadol, and ofloxacin) in plasma [73][74][75][76], serum [75,77], and cells [78], and up to micromolar concentrations of the persistent pollutants polychlorinated biphenyls or of thiobencarb sulfoxide in culture media [79,80] has been performed. Although much less used, as it can be observed in Table 2, SLE, LPME, and microdialysis have also been employed for the preparation of samples for sensitive chiral CE.…”

Stereoselective determination of drugs and metabolites in body fluids, tissues and microsomal preparations by capillary electrophoresis (2000–2010)

“…Compared to the previous decade, during which mostly uncharched CDs were employed [26], we noted a strong increase of the use of charged CDs. S-␤-CD, with 7-11 mol sulfate/mol ␤-CD, was most often used [58,60,63,69,71,79,80,83,95,97,99,101,108,110,118,123,131,134,135,139,[154][155][156][157][158][159][160][161][162][163][164][165][166][167][168][169] whereas the better defined highly sulfated CD derivatives (HS-␤-CD and HS-␥-CD [170]) were only used in a few assays [50,51,72,111,144,145]. These and other selectors, such as phosphated-␥-CD (PH-␥-CD) [94,106,126], carboxymethyl-␤-CD (CM-␤-CD) or carboxymethyl-␥-CD (CM-␥-CD) …”

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

“…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.…”

“…Para o desenvolvimento desses métodos estão sendo empregadas as técnicas de HPLC e CE. As referências já citadas nesse texto 44,48,52,[89][90][91][92][93][94][95]100,104,110 e algumas outras publicações recentes [121][122][123][124] demostram o grande envolvimento desses grupos na análise enantiosseletiva de fármacos e metabólitos em materiais biológi-cos. Como as análises são feitas em matrizes biológicas complexas e analitos presentes em quantidades muito baixas, também estão sendo desenvolvidos e validados novos procedimentos de preparação da amostra como, por ex., a microextração em fase sóli-da 110 . Graças a esses métodos desenvolvidos, vários estudos de disposição cinética estão sendo realizados, possibilitando estabelecer a influência de várias doenças e aspectos genéticos na disposição cinética de fármacos quirais, sendo citados apenas os mais recentes [125][126][127][128][129] .…”