HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ANALYSIS OF SOME ANTIARRHYTHMIC DRUGS IN HUMAN SERUM USING CYANOPROPYL DERIVATIZED SILICA PHASE

A high performance liquid chromatographic determination of antiarrhyth mic agents: propafenone (PPF) with its principal active metabolite 5-h ydroxypropafenone (5-OHPPF), amiodarone (AD) with an active metabolite desethylamiodarone (DEAD), mexiletine (MEX) and diltiazem (DILT) in h uman serum is presented. The compounds are separated on Supelcosil LC- CN column at ambient temperature under isocratic conditions. For PPF, 5-OHPPF, MEX and DILT analysis the mobile phase: CH3CN:H2O:0.5 M KH2PO 4 (360:620:20 v/v) is pumped at a flow rate of 1.8 mL/min and the ultr aviolet detection is performed at 210 nm. AD and DEAD are eluted with stronger mobile phase: CH3OH:CH3CN:H2O:0.5 M KH2PO4 (480:136:360:24 v/ v) at a flow rate of 1.5 mL/min and detected at 240 nn. Sample prepara tion is based on simple liquid-liquid extraction from acidified serum for AD and DEAD and on liquid-liquid extraction from alkalized serum f ollowed by back extraction for PPF, 5-OHPPF, MEX and DILT analysis. Se nsitivity of the assay was set at 5 ng/mL, for PPF and MEX and at 10 n g/mL for 5-OHPPF, DILT, AD and DEAD. Coefficient of variation for intr a- and interassay precision was below 10% for all the tested compounds in all the tested concentrations. The method is convenient for therap eutic monitoring of those four antiarrhythmics. Described assay may be easily adapted for the determination of verapamil, gallopamil, quinid ine, flecainide and a few beta-blockers.