Simultaneous Determination of Dofetilide and Amlodipine in Plasma by HPLC

Abstract

Dofetilide is a Class III antiarrhythmic drug useful in the management of atrial fibrillation but also known to prolong the QT interval on the ECG and to induce malignant ventricular tachyarrhythmias such as torsades de pointes (TDP). Drugs with calcium channel-blocking properties contribute to decrease the incidence of TDP. Amlodipine is a dihydropyridine calcium channel antagonist. Considering the potentially safe and useful combined use of dofetilide and amlodipine, we undertook drug biotransformation studies. To perform studies aiming to evaluate the possible pharmacokinetic interaction between these drugs, a unique sensitive HPLC assay able to quantify both drugs simultaneously was required. A sensitive and specific HPLC method using a tandem of UV/fluorescence detection was described for the analysis of amlodipine and dofetilide in plasma. The within-day and between-day precision studies showed good reproducibility with coefficients of variation less than 10% for all the analytes. The limits of detection were 0.5 ng/mL and 0.25 ng/mL and the limit of quantification were 1.7 ng/mL and 0.8 ng/mL for dofetilide and amlodipine respectively. This new method could be of great value in many applications such as in vitro and in vivo pharmacokinetic and drug-drug interactions studies, as well as therapeutic drug monitoring.