The enantiomers of metoprolol were determined in plasma samples after direct resolution on a silica bonded α1-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 ofR- andS-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.
