A liquid chromatography-tandem mass spectrometry analysis of nine cytochrome P450 probe drugs and their corresponding metabolites in human serum and urine.
Anal Bioanal Chem
; 409(1): 251-268, 2017 Jan.
Article
em En
| MEDLINE
| ID: mdl-27734142
ABSTRACT
Cocktail phenotyping using specific probe drugs for cytochrome P450 (CYP) enzymes provides information on the real-time activity of multiple CYPs. We investigated different sample preparation techniques and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with simple protein precipitation for the analysis of nine CYP probe drugs and their metabolites in human serum and urine. Specific CYP probe drugs (melatonin, CYP1A2; nicotine, CYP2A6; bupropion, CYP2B6; repaglinide, CYP2C8; losartan, CYP2C9; omeprazole, CYP2C19 and CYP3A4; dextromethorphan, CYP2D6; chlorzoxazone, CYP2E; midazolam, CYP3A4) and their main metabolites, with the exception of 3'-hydroxyrepaglinide, were quantified in human serum and urine using the developed LC-MS/MS method. The analytical method was fully validated showing high selectivity, linearity, acceptable accuracy (85-115 %) and precision (2-19 %) and applied to a pharmacokinetic study in four healthy volunteers after oral administration of drugs given as a cocktail. All probe drugs and their metabolites (totally 19 analytes) were detected and quantified from human serum and urine over the time range of 1 to 6 h after oral administration. Therefore, the proposed method is applicable for drug interaction and CYP phenotyping studies utilizing a cocktail approach. Graphical Abstract Workflow overwiew of cocktail CYP-phenotyping study.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Preparações Farmacêuticas
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Cromatografia Líquida
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Sistema Enzimático do Citocromo P-450
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Espectrometria de Massas em Tandem
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article