A method for analyzing flecainide in plasma was developed and assessed. Based on the use of C18 extraction columns eight or fewer times, the rapid and simple extraction procedure provided consistent, high-efficiency flecainide extraction (>85%). Using reverse-phase, high-performance liquid chromatography with fluorometric detection, flecainide acetate was detectable to approximately 15 ng/ml. Retention times of the internal standard and flecainide were 8.9 to 9.2 and 9.8 to 10.4 minutes, respectively, and short sample preparation and run times enabled results to be delivered within 2 to 3 hours of receiving samples. The assay was linear for the standard range 20 ng/ml to 2 microg/ml (r2 with three standards, >0.999) and delivered a high level of accuracy. Quality control concentrations obtained from eight assays consistently fell within 5% of nominal values (100 ng/ml and 1 microg/ml). Based on four assays, the assay was also reproducible with calculated-between and within-assay coefficients of variation of less than 1% and 3%, respectively. The authors found that the performance of this assay was excellent and that the solid-phase extraction technique was simple, rapid, and cost effective.