Determination of mexiletine in biological fluids by high-performance liquid chromatography

A high-performance liquid chromatographic method for the determination of the anti-arrhythmic drug mexiletine in human plasma, urine, and cerebrospinal fluid is described. Following extraction with diethyl ether, mexiletine and the internal standard 4-methylmexiletine were derivatized with 2,4-dinitrofluorobenzene. Analyses were performed using an alternating on-column enrichment technique on small Perisorb RP-2 30-40 micrometers pre-columns with pre-column backflushing for direct injection onto the analytical column of Spherisorb ODS 5 micrometers. Complete separation from endogenous constituents of plasma, urine or cerebrospinal fluid was achieved by isocratic reversed-phase ion-pair chromatography with 1-heptanesulfonic acid (0.005 M; PIC B7)-acetonitrile-tetrahydrofuran (42:48:10, v/v) as eluent. Interferences from other drugs were not observed. The limit of detection was 10 ng/ml (C.V. 6.5%). Day-to-day coefficients of variation were below 9%. The applicability of this rapid method for pharmacokinetic studies and clinical routine is demonstrated.