Dronedarone is a derivative of amiodarone – a popular antiarrhythmic drug. It was developed to overcome the limiting iodine-associated toxicities of amiodarone. Debutyldronedarone is a major circulating active metabolite of dronedarone in humans. To investigate the pharmacokinetics of dronedarone, a rapid, simple, and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated to simultaneously determine dronedarone and debutyldronedarone in human plasma using amiodarone as internal standard (IS). Acetonitrile with IS was used to precipitate proteins from a 5-μL aliquot of plasma. Effective chromatographic separation was performed on a CAPCELL PAK C18MG (1 mm × 4.6 mm, 5 μm) column with gradient elution (5 mmol/L ammonium acetate-acetonitrile, with each phase containing .2% acetic acid) at a flow rate of .7 mL/min. Complete separation was achieved within 5.5 min. Detection was carried out on an tandem mass spectrometer in multiple reaction monitoring mode using a positive atmospheric pressure chemical ionization interface. A lower limit of quantification of .2 ng/mL was achieved for both dronedarone and debutyldronedarone, with acceptable precision and accuracy. The linear range of the method was from .2 to 2 ng/mL for each analyte. Intra- and inter-day precisions were lower than 7.2% in relation to relative standard deviation, while accuracy was within ±5.1% in terms of relative error for analytes. Our findings demonstrate the successful application of the validated LC–MS/MS method to a pharmacokinetic study after a single oral administration of 4 mg dronedarone to six healthy volunteers.An LC-MS/MS method was validated to determine dronedarone and debutyldronedarone in human plasma. The method has an LLOQ of .2 ng/mL for both analytes. Sample preparation was simple and quick with acetonitrile protein precipitation. The method was applied to a pharmacokinetic study of dronedarone in humans..
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