Amiodarone Analysis by Capillary Electrophoresis

Abstract

Amiodarone is a broad spectrum antiarrhythmic medication. Toxicity symptoms can occur at high serum levels of this drug; thus the level of this drug requires routine monitoring. Because this drug is very hydrophobic, it is difficult to analyze by both HPLC and capillary electrophoresis (CE). A simple method for measuring amiodarone (A) by CE without sample extraction is described. It is based on separation of the drug in a strong phosphate buffer 170 mmol/L, pH 5.9, with added ethanol, and stacking after acetonitrile deproteinization. The ethanol in the phosphate buffer aids to solubilize the drug, migrate it from the neutral to the cationic molecules region, and to separate it from its metabolite, desethylamiodarone (D). The metabolite D is pharmacologically active; has the similar therapeutic range as the parent drug; similar ultra violet absorption; and at steady state is present at equal ratio. Based on these facts, we choose for routine analysis, conditions where the drug and its metabolite co‐elute. These conditions improved the detection limits, shortened the analysis time (<10 min), and avoided the mathematical addition of the two values to arrive at the therapeutic level. The analysis by CE compared well to that by HPLC, r=0.9. The therapeutic range of the combined values of the amiodarone and the metabolite was estimated to be 1.2–4 mg/L.

Keywords:

• Stacking
• Transient pseudo‐isotachophoresis
• Antiarrhythmic drug