Stereoselective analysis of carvedilol in human plasma and urine using HPLC after chiral derivatization

An enantioselective high‐performance liquid chromatographic method for the analysis of carvedilol in plasma and urine was developed and validated using (‐)‐menthyl chloroformate (MCF) as a derivatizing reagent. Chloroform was used for extraction, and analysis was performed by HPLC on a C18 column with a fluorescence detector. The quantitation limit was 0.25 ng/ml for S(−)‐carvedilol in plasma and 0.5 ng/ml for R(+)‐carvedilol in plasma and for both enantiomers in urine. The method was applied to the study of enantioselectivity in the pharmacokinetics of carvedilol administered in a multiple dose regimen (25 mg/12 h) to a hypertensive elderly female patient. The data obtained demonstrated highest plasma levels for the R(+)‐carvedilol ( AUC   SS 0–1275.64 vs 37.29 ng/ml). The enantiomeric ratio R(+)/S(−) was 2.03 for plasma and 1.49 for urine ( Ae 0–12 17.4 vs 11.7 µg). Copyright © 2008 John Wiley & Sons, Ltd.