ENANTIOSELECTIVE ANALYSIS OF SOTALOL IN PLASMA BY REVERSED-PHASE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY USING DIASTEREOMERIC DERIVATIVES

A procedure for the concurrent determination of the (+)- and (-)-enant iomers of sotalol in plasma using high-performance liquid chromatograp hy of diastereomeric derivatives is described. Sotalol is extracted fr om a 0.5-ml aliquot of plasma at pH 9.3 using ethyl acetate. Atenolol is used as the internal standard. The ethyl acetate is removed under v acuum, and the residue derivatized with R-(-)-1-(l-naphthyl)ethyl isoc yanate (NEIC, 0.005% in chloroform) in the presence of trace quantitie s of carbonate buffer. The chloroform is removed, the residue reconsti tuted in mobile phase (acetonitrile-water, 39:61, v/v), and an aliquot injected into the HPLC column. A C-18 trapping column is used to reta in excess derivatizing reagent. While the derivatives are separated on a C-18 analytical column with the isocratic mobile phase mentioned ab ove at 1.5 ml/min, the column-switching allows back-hushing of the tra pping column to prepare for the next injection. The derivatives were d etected using a fluorescence detector with excitation wavelength 280 n m and emission wavelength 320 MI. The method was fully validated, and shown to have excellent linearity, specificity, sensitivity, accuracy and precision. It has been applied to the determination of(+)- and (-) -sotalol in plasma from twelve subjects dosed with racemic sotalol.