Analytical Sciences

Abstract − Analytical Sciences, 20(9), 1307 (2004).

A Rapid HPLC Assay for the Simultaneous Determination of Propafenone and Its Major Metabolites in Human Serum
Minoo AFSHAR and Mohammadreza ROUINI
Biopharmaceutics and Pharmacokinetics Division, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, 14155-6451, Tehran, Iran
A rapid and specific HPLC method has been developed and validated for the simultaneous determination of propafenone, an antiarrhythmic agent, and its major metabolites in human serum. The sample preparation was a simple deproteinization with a mixture of ZnSO4 and methanol, yielding almost 100% recoveries of three compounds. Separation was developed on a reverse-phase tracer excel C18 column (25 × 0.46 cm i.d., 5 µm), using an acetonitrile-phosphate buffer gradient at a flow rate of 1.7 ml min-1, and UV detection of 210 nm. The calibration curves were linear (r2 > 0.999) in the concentration range of 10 - 750 ng ml-1. The lower limit of quantification was 10 ng ml-1 for all of the compounds studied. The within and between day precisions in the measurement of QC samples at four tested concentrations were in the range of 1.4 - 8.1% and 4.2 - 11.5% RSD, respectively. The developed procedure was applied to assess the pharmacokinetics of propafenone and its major metabolites following administration of a single 300 mg oral dose of propafenone hydrochloride to three healthy male volunteers.