High performance liquid chromatographic analysis of the antiarrhythmic drugs procainamide, disopyramide, quinidine, propranolol and metabolites from serum extracts.

We describe a method for the simultaneous high performance liquid chromatographic determination of several antiarrhythmic drugs and some of their metabolites after extraction from 2.5 mL of spiked pooled sera. The extracts were applied to a C8 reversed phase column. Nine compounds of interest were resolved within the 30 minute run. An initial mobile phase of 80% phosphate (25 mmol/L, pH 3.5), 20% organic (acteonitrile:methanol, 2:3) was maintained for 2 min at which time a linear gradient was used to change the mobile phase to 30% phosphate, 70% organic at 20 min after injection. This composition was maintained from an additional 5 min. Absorbance at 212 nm was used for detection. Peak area ratios of drug to internal standard (N-propionylprocainamide) were used for quantitation. The relative standard deviations (and mean solute concentrations) of daily duplicate determinations for 15 days are: procainamide, 5.1% (5.9 mg/L); N-acetylprocainamide, 9.3% (6.0 mg/L); Mono-N-dealkyldisopyramide, 3.7% (4.1 mg/L); disopyramide, 4.3% (4.0 mg/L); quinidine, 4.5% (6.5 mg/L); and propranolol, 5.1% (0.097 mg/L). Dihydroquinidine and 4-hydroxypropranolol were also resolved but not quantitated.