Gas chromatographic determination of metoprolol in human plasma

A method for the determination of metoprolol at concentrations down to 10 ng/ml in human plasma is described. After addition of oxprenolol as internal standard, both compounds are extracted into diethyl ether--dichloromethane (4:1, v/v) at basic pH, transferred into an acidic aqueous solution and back-extracted at basic pH into diethyl ether--dichloromethane. They are then derivatized with heptafluorobutyric anhydride. The derivatives are quantitatively determined by gas chromatography using a 63Ni electron-capture detector. The linearity was demonstrated, and the technique was formally validated in the concentration range 10-500 ng/ml. The technique was applied in a study of the bioavailability of metoprolol after oral administration to man; mean plasma concentrations are reported.