High-performance liquid chromatographic determination of 12 antiarrhythmic drugs in plasma using solid-phase column extraction.

Monitoring of plasma concentrations of antiarrhythmic drugs may assist in individualizing dosage regimens and in assessing patient compliance. A rapid high-performance liquid chromatographic assay using solid-phase column extraction was developed for the following antiarrhythmic drugs: amiodarone, aprindine, disopyramide, flecainide, lidocaine, lorcainide, mexiletine, procainamide, propafenone, sotalol, tocainide, and verapamil. As most of the antiarrhythmic drugs are basic compounds, good adsorption on the extraction columns was obtained by alkalinization; aprindine, however, was applied at neutral pH and amiodarone at pH 3.5. After washing with water, the compounds were eluted with methanol, but amiodarone was eluted with a mixture of acetonitrile and acetate buffer at pH 5 (8/2, vol/vol). Most of the eluates were evaporated to dryness and reconstituted in the mobile phase; for amiodarone, disopyramide, and tocainide, direct injection onto the column was performed. Separation was done on a Spherisorb hexyl 5 mu column (150 x 4.6 mm I.D.) and the mobile phases consisted of mixtures of acetonitrile or methanol with phosphate or acetate buffers at different pH values. Detection was performed by UV or fluorescence detector. Coefficients of variation were lower than 10% with good recovery and linearity in the expected therapeutic ranges.