Enantioselective CE method for pharmacokinetic studies on ibuprofen and its chiral metabolites with reference to genetic polymorphism.
A stereospecific CE method was elaborated for the quantification of ibuprofen enantiomers and their major phase I metabolites: 2'-hydroxy-ibuprofen and 2'-carboxy-ibuprofen in plasma and urine. Optimal temperature and pH of BGE were established to obtain complete separation of eight ibuprofen chiral compounds and (+)-S indobufen, applied as an internal standard, during one analytical run. After isolation from biological matrices using SPE on an octadecyl stationary phase, the analytes were separated and resolved up to 10 min in a silica capillary filled with BGE, consisting of heptakis 2,3,6-tri-O-methyl-beta-CD in triethanolamine-phosphate buffer, pH 5.0. Complete enantioseparation of the all analytes confirmed specificity of the method. The calibration curves were linear in the range of 0.1-25.0 mg/L for IBP enantiomers and their chiral metabolites in 0.5 mL of plasma and 1.0-200.0 mg/L in 0.05 mL of urine. Following SPE procedure, recovery of the chiral analytes from the two media was in the ranges of 82-87%, 90-95% and 70-76% for ibuprofen, 2'-hydroxy-ibuprofen and 2'-carboxy-ibuprofen enantiomers, respectively. The validated method was successfully applied in pharmacokinetic investigations of IBP enantiomers as well as free chiral metabolites in reference to the genetic polymorphism of CYP450 2C isoenzymes.
Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poznań, Poland. glowka@amp.edu.pl
Franciszek
F
Główka
Marta
M
Karaźniewicz
D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D007052:Ibuprofen / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000652:urine; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic; D013237:Stereoisomerism; D047392:beta-Cyclodextrins
D047392:beta-Cyclodextrins; C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System; D007052:Ibuprofen