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Radioreceptor Assay of Metoprolol in Human Plasma: Comparison with an Enantiospecific High-Performance Liquid Chromatographic (HPLC) Procedure

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Abstract

Plasma concentrations of metoprolol after acute and repetitive administration of R/S-metoprolol to healthy volunteers were measured by a β-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 β1-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.

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Authors and Affiliations

  1. Pharmakologisches Institut für Naturwissenschaftler, Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, Geb. 75A, D-6000, Frankfurt/M. 70, F.R.G

    Hildegard Spahn

  2. Zentrum der Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-6000, Frankfurt/M. 70, F.R.G

    Anton Wellstein

  3. National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892

    Anton Wellstein

Authors
  1. Hildegard Spahn
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  2. Anton Wellstein
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  3. Gabriele Pflugmann
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  4. Ernst Mutschler
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  5. Dieter Palm
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Spahn, H., Wellstein, A., Pflugmann, G. et al. Radioreceptor Assay of Metoprolol in Human Plasma: Comparison with an Enantiospecific High-Performance Liquid Chromatographic (HPLC) Procedure. Pharm Res 6, 152–155 (1989). https://doi.org/10.1023/A:1015984626848

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  • DOI: https://doi.org/10.1023/A:1015984626848

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