Quantitative high-performance liquid-chromatographic method for determining disopyramide (Norpace) in serum

We report a high-performance liquid-chromatographic method for measuring disopyramide (Norpace, Searle) in serum. The drug is extracted from 0.5 ml of serum into chloroform containing the internal standard p-chlorodisopyramide, separated on a reversed-phase octadecylsilyl column at room temperature, and detected at 254 nm. The method is sensitive to 0.2 mg of disopyramide per liter, with a linear response to at least 10 mg/liter. Within-day precision (CV) for frozen serum pools is 8.3 (n = 21) and (n = 22) at mean concentrations of 2.6 and 5.9 mg/liter, respectively. Day-to-day precision (CV) is 9.4 (n = 80) and 9.3 (n = 29) at mean concentrations of 2.8 and 6.7 mg/liter, respectively. Recoveries for disopyramide in serum averaged 98% over the linear range when compared against an aqueous standard taken through the entire analytical procedure. The method is relatively specific, as evidenced by interference studies with over 85 drugs.