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 diheptafluorobutyl alpredolol which were then separated and detected by 3% SE-30 packed glass column (2m×3mm)equipped with ECD. The detection limit was 1 ng/ml and the linearrangewas 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 then 8% and 7%, respectively. The method has been applied to investigate the Pharmacokinetics and bioavailability of metoprolol and also applied to clinical monitoting of metoprolol levels in patients.