Measurement of Carvedilol Enantiomers in Human Plasma and Urine Using S‐Naproxen Chloride for Chiral Derivatization
- 1 January 1990
- journal article
- research article
- Published by Wiley in Archiv der Pharmazie
- Vol. 323 (8), 465-469
- https://doi.org/10.1002/ardp.19903230805
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.This publication has 7 references indexed in Scilit:
- Radioreceptor Assay of Metoprolol in Human Plasma: Comparison with an Enantiospecific High-Performance Liquid Chromatographic (HPLC) ProcedurePharmaceutical Research, 1989
- S-(+)-naproxen chloride as acylating agent for separating the enantiomers of chiral amines and alcoholsArchiv der Pharmazie, 1988
- Enantiospecific High-Performance Liquid Chromatographic (HPLC) Determination of Baclofen and Its Fluoro Analogue in Biological MaterialPharmaceutical Research, 1988
- Pharmacokinetics and bioavailability of carvedilol, a vasodilating beta-blockerEuropean Journal of Clinical Pharmacology, 1987
- Activated α-alkyl-α-arylacetic acid enantiomers for stereoselective thin-layer chromatographic and high-performance liquid chromatographic determination of chiral aminesJournal of Chromatography B: Biomedical Sciences and Applications, 1984
- PharmacokineticsPublished by Informa UK Limited ,1982
- Noncompartmental Determination of the Steady‐State Volume of DistributionJournal of Pharmaceutical Sciences, 1979