Measurement of Carvedilol Enantiomers in Human Plasma and Urine Using S‐Naproxen Chloride for Chiral Derivatization

Abstract

The enantiospecific procedure for assaying carvedilol includes the extraction of the drug from plasma or urine with diisopropylether after alkalization of the sample with pH 9.8 buffer. After evaporation of the org. solvent a chiral derivatization is performed using S-(+)-naproxen chloride. The HPLC separation of the diastereomeric amides is possible on a silica gel stationary phase with a mixture of n-hexane, dichloromethane, and ethanol as mobile phase. Detection of the products is performed by fluorescence measurement at 285/355 nm. Preliminary pharmacokinetic studies after i.v. infusion of racemic compound to healthy volunteers showed that the concentrations of the R-(+)-enantiomer exceeded those of the S-(−)-enantiomer. Overall, both carvedilol enantiomers exhibited a high clearance with preference for the S-enantiomer. The difference was even more expressed after p.o. dosage indicating a stereoselective first-pass effect with higher extraction of the levorotatory enantiomer, which is more potent with respect to β-adrenoceptor antagonistic activity.