A simple HPLC method has been developed to measure the antiarrhythmic agent penticainide and its N-desalkyl metabolite in biological fluids. Solvent extraction of a small (200 microL) sample volume with direct analysis of the extract is used to measure the plasma and urinary concentrations of these compounds attained during chronic therapy, although a larger sample volume (1.0 mL) and prior concentration of the extract are required for single oral dose work. In each case chromatographic analysis is performed using a microparticulate (5 microns) silica column and methanolic ammonium perchlorate (10 mM, pH 6.7) as eluent with UV detection (260 nm). No endogenous sources of interference have been encountered and potential interference from other drugs is minimal.