AbstractA direct, isocratic and simple liquid chromatographic method is described for the enantiomeric separation of propafenone (PRO) and its major metabolite, 5‐hydroxypropafenone, using a cellulose tris‐3,5‐dimethylphenyl carbamate (Chiralcel ODS) column. The sterochemical separation factor (α) obtained was 1.14 and the maximum stereochemical resolution factor (R) was 0.80 when using a mobile phase consisting of hexane: 2‐propanol: diethylamine (90:10:0.4) at 23°C. The hydroxy metabolite could not be successfully separted into its corresponding enantiomers under these chromatographic conditions. The method has been used to determine and identify the enantiomers of PRO and its hydroxy metabolite in a ser