[Determination of metoprolol in plasma by gas chromatography and electron-capture detection]

A method is described to determine metoprolol in plasma by GC-ECD. Metoprolol and alprenolol (internal standard) reacted rapidly with heptafluorobutyric anhydride under the catalysis of tetrahydrofuran (THF) after being extracted from plasma with cyclohexane. The derivatives produced quantitatively were identified by GC-MSD to be diheptafluorobutyl metoprolol and dihepatafluorobutyl alpredolol which were then separated and detected by 3% SE-30 packed glass column (2m x 3 mm) equipped with ECD. The detection limit was 1 ng/ml and the linear range was 10-1500 ng/ml (r = 0.9993). Average recovery from spiked plasma was 97.30%. The coefficient of variation of day-to-day and within-day were less than 8% and 7%, respectively. The method has been applied to investigate the pharmacokinetics and bioavailability of metoprolol and also applied to clinical monitoring of metoprolol levels in patients.