RESUMO
Plasma concentrations of metoprolol after acute and repetitive administration of R/S-metoprolol to healthy volunteers were measured by a beta-adrenoceptor subtype-specific radioreceptor assay (RRA) and by an enantiospecific high-performance liquid chromatographic (HPLC) method. In the RRA, R/S-metoprolol showed a 20-fold beta 1-subtype selectivity: the S-(-)-enantiomer was 35-fold more potent than the R-(+)-enantiomer. A comparison between S-(-)-metoprolol concentrations detected in the plasma samples by HPLC and those detected by RRA yielded a 1/1 relationship, indicating that active metabolites are not present to a significant extent. These results were independent of the widely scattering metabolic clearance of metoprolol (with the potential of differences in the rate and extent of formation of active metabolites) in the volunteers. In general, HPLC methods can be validated by comparison with RRA in order to clarify whether active metabolites are present and--on the basis of the Ki value from RRA--whether the detection limit of the physicochemical procedure is sufficient to cover the therapeutically relevant range.
Assuntos
Metoprolol/sangue , Animais , Cromatografia Líquida de Alta Pressão , Humanos , Técnicas In Vitro , Taxa de Depuração Metabólica , Ensaio Radioligante , Ratos , Receptores Adrenérgicos beta/metabolismo , EstereoisomerismoRESUMO
A method is described that makes possible the rapid determination of the enantiomers of beta-blocking agents. After extraction from urine samples (at pH 9.9) using toluene, the enantiomers are derivatised with S-(+)-benoxaprofen chloride. The chromatographic separation can be performed on thin-layer plates with toluene-acetone as mobile phase. The derivatives can be detected by measuring the fluorescence (lambda ex = 313 nm,lambda em = 365 nm).
