An effective and simple SPE-HPLC assay for monitoring of clinically applied antiarrhythmics and their metabolites in serum samples was developed. In particular, the generally used SPE step has been modified for the clean-up and preconcentration procedure of clinical samples. Extraction recoveries for all analyzed compounds were in the range 81.4-90.7% for the concentration level m g.ml^-1 of serum.