Enantioselective determination of metoprolol in plasma by liquid chromatography on a silica-bonded α 1-acid glycoprotein column

Abstract The enantiomers of metoprolol were determined in plasma samples after direct resolution on a silica bonded α 1 -acid glycoprotein column. Metoprolol was extracted from plasma into a diethyl ether-dichloromethane mixture and after back extraction to dilute phosphoric acid and adjustment of pH the sample was injected on a Chiral- AGP column for separation of R - and S -metoprolol. It was possible to measure down to 2 nmol per litre plasma with a relative standard deviation of less than 15% by use of gradient elution and fluorescence detection. The analytical method was employed to study the pharmacokinetics of the metoprolol enantiomers after administration of the racemate to humans.