Phenotype analysis of cytochrome P450 2C19 in Chinese subjects with mephenytoin S/R enantiomeric ratio in urine measured by chiral GC.
A chiral gas chromatographic method with FID was developed for the determination of S- and R-mephenytoin in human urine. The assay is linear from 25 to 800 ng/mL for each enantiomer and the limit of detection and limit of quantitation were 12 and 25ng/mL for each enantiomer, respectively. The method affords average recoveries of 74.41 +/- 3.93% and 73.78 +/- 3.02% for S- and R-mephenytoin, respectively. The method allows the phenotype study of CYP2C19 in Chinese subjects. The phenotype pattern of 90 Chinese volunteers was determined, in which 26 volunteers received phenotyping and genotyping tests. The results of phenotype analysis showed that the interindividual variation was marked. The mephenytoin S/R enantiomeric ratios in urine of 11 volunteers were > or = 0.95 and identified as poor metabolizers. The frequency of poor metabolizers was 12.2% in the Chinese subjects tested. A good relationship between phenotype and genotype analysis of CYP2C19 was observed.
Yao
T W
TW
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310031, People's Republic of China.
Zeng
S
S
Wang
T W
TW
Chen
S Q
SQ
D001189:Aryl Hydrocarbon Hydroxylases; D044466:Asian People / Q000235:genetics*; D002138:Calibration; D002681:China; D002849:Chromatography, Gas / Q000379:methods*; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008617:Mephenytoin / Q000737:chemistry / Q000652:urine*; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D008617:Mephenytoin