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Enantiospecific separation and quantitation of mephenytoin and its metabolites nirvanol and 4'-hydroxymephenytoin in human plasma and urine by liquid chromatography/tandem mass spectrometry.
- Source :
-
Rapid communications in mass spectrometry : RCM [Rapid Commun Mass Spectrom] 2006; Vol. 20 (3), pp. 463-72. - Publication Year :
- 2006
-
Abstract
- A sensitive method using enantiospecific liquid chromatography/tandem mass spectrometry detection for the quantitation of S- and R-mephenytoin as well as its metabolites S- and R-nirvanol and S- and R-4'-hydroxymephenytoin in plasma and urine has been developed and validated. Plasma samples were prepared by protein precipitation with acetonitrile, while urine samples were diluted twice with the mobile phase before injection. The analytes were then separated on a chiral alpha(1)-acid glycoprotein (AGP) column and thereafter detected, using electrospray ionization tandem mass spectrometry. In plasma, the lower limit of quantification (LLOQ) was 1 ng/mL for S- and R-4'-hydroxymephenytoin and S-nirvanol and 3 ng/mL for R-nirvanol and S- and R-mephenytoin. In urine, the LLOQ was 3 ng/mL for all compounds. Resulting plasma and urine intra-day precision values (CV) were <12.4% and <6.4%, respectively, while plasma and urine accuracy values were 87.2-108.3% and 98.9-104.8% of the nominal values, respectively. The method was validated for plasma in the concentration ranges 1-500 ng/mL for S- and R-4'-hydroxymephenytoin, 1-1000 ng/mL for S-nirvanol, and 3-1500 ng/mL for R-nirvanol and S- and R-mephenytoin. The validated concentration range in urine was 3-5000 ng/mL for all compounds. By using this method, the metabolic activities of two human drug-metabolizing enzymes, cytochrome P450 (CYP) 2C19 and CYP2B6, were simultaneously characterized.<br /> (Copyright (c) 2006 John Wiley & Sons, Ltd.)
- Subjects :
- Chromatography, Liquid
Humans
Mass Spectrometry
Mephenytoin blood
Mephenytoin chemistry
Mephenytoin isolation & purification
Mephenytoin urine
Reference Standards
Reproducibility of Results
Sensitivity and Specificity
Stereoisomerism
Mephenytoin analogs & derivatives
Mephenytoin analysis
Mephenytoin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0951-4198
- Volume :
- 20
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Rapid communications in mass spectrometry : RCM
- Publication Type :
- Academic Journal
- Accession number :
- 16395737
- Full Text :
- https://doi.org/10.1002/rcm.2324