Enantioselective separation and determination of miconazole in rat plasma by chiral LC-MS/MS: application in a stereoselective pharmacokinetic study.
Anal Bioanal Chem
; 409(27): 6315-6323, 2017 Nov.
Article
em En
| MEDLINE
| ID: mdl-28852798
ABSTRACT
Miconazole has one chiral center, and consists of two enantiomers. In this study, a novel chiral liquid chromatography-tandem mass spectrometry method was developed for enantioselective separation and determination of miconazole in rat plasma. For the first time, the enantioselective pharmacokinetics of miconazole was investigated by the current method. Firstly, attempts were made to separate the enantiomers in reversed-phase mode with a mobile phase that was mass spectrometry compatible. Baseline separation was achieved on a Chiralpak IC column with a mobile phase composed of acetonitrile and aqueous ammonium hydrogen carbonate (5 mM; 8020, v/v). Data were acquired in multiple reaction monitoring mode with positive electrospray ionization by triple-quadrupole mass spectrometry. Then, overall method validation regarding the linearity, accuracy, precision, extraction recovery, matrix effect, and stability of each enantiomer was performed, and acceptable results were obtained for all of these. Finally, the method developed was applied in an enantioselective pharmacokinetic study of miconazole enantiomers in rats after oral administration of racemic miconazole at doses of 5 and 10 mg/kg. The results demonstrated that (-)-(R)-miconazole had a higher concentration than (+)-(S)-miconazole in plasma, with a ratio of 1.3-1.7 for both doses. This is the first experimental evidence of enantioselective behavior of miconazole in vivo, and provides a reference for clinical practice and encourages further research into miconazole enantioselective metabolism and drug interactions. Graphical Abstract A stereoselective pharmacokinetic study of the miconazole enantiomers was investigated using a novel chiral liquid chromatography-tandem mass spectrometry method. Baseline separation was achieved on Chiralpak IC column, and Chiralcel OJ column was used to collect single enantiomer. A significant difference between the two enantiomers was observed in view of the plasma concentration.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Cromatografia Líquida de Alta Pressão
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Espectrometria de Massas em Tandem
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Miconazol
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Antifúngicos
Limite:
Animals
Idioma:
En
Revista:
Anal Bioanal Chem
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China