Abstract: A rapid, sensitive and simple high performance liquid chromatographicmethod for the simultaneous determination of propafenone (PPF) and its metabolites(5-hydroxypropafenone, 5-OHP; N-depropylpropafenone, NDP) in serum hasbeen developed. Separation of PPF, 5-OHP and NDP was achieved by reversed phasechromatography using a mobile phase consisting of 57% methanol and 43% 10 mmol/Lpotassium dibasic phosphate (pH 2.7)at a flow rate of 1.0 mi/rain on a 5μm ODS-C18column. The eluent was monitored at 254 nm. The method showed a good linearity. The recoveries of PPF, 5-OHP and NDP werefound to be 99.54±2. 13%, 100.02±3.66% and 100.48±3.10%, respectively. Precisionstudies for both within day and day-to-day at different concentrations provided RSDvalues of less than 5%. Some commonly used drugs can be determined in the same procedurewithout interference except phenytoin. This method is well adapted to the therapeuticmonitoring of PPF treated patients, as well as for pharmacokinetic studies.