Document Detail


Development of a HPLC method for the determination of losartan urinary metabolic ratio to be used for the determination of CYP2C9 hydroxylation phenotypes.
MedLine Citation:
PMID:  23093260     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Abstract Background: Losartan is metabolized to losartan carboxylic acid (E-3174) by the polymorphic cytochrome CYP2C9. The aim of the study was to develop a high-performance liquid chromatographic (HPLC) method with fluorescence detection for simultaneously measuring losartan and its metabolite E-3174 in urine to evaluate the losartan urinary metabolic ratio (MR: losartan/E-3174) for CYP2C9 phenotyping in humans. Methods: The compounds were separated in a reversed-phase chromatographic column and detected by fluorescence at a wavelength of 250 nm for excitation and of 370 nm for emission. Results: No analytical interferences with endogenous compounds were found, and the extraction recoveries were over 88%. Limits of quantification of 2 ng mL-1 for losartan and 5 ng mL-1 for E-3174 were achieved, as well as good reproducibility with coefficients of variation of <9% in all cases. Analyses with the present HPLC method show significant differences (p<0.05) in losartan MRs between the four CYP2C9 genotype groups in 13 Spanish healthy volunteers. Conclusions: The method developed is simple and affordable, as well as sensitive and reliable to calculate the MR. Therefore, it appears to be useful for CYP2C9 phenotyping using losartan as a drug test in populations, such as Hispanics with different allele combinations.
Authors:
Pedro Dorado; Esther Machín; Fernando de Andrés; María-Eugenia G Naranjo; Eva M Peñas-Lledó; Adrián Llerena
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-25
Journal Detail:
Title:  Drug metabolism and drug interactions     Volume:  -     ISSN:  0792-5077     ISO Abbreviation:  Drug Metabol Drug Interact     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-10-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8904736     Medline TA:  Drug Metabol Drug Interact     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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