Separation and quantitation of azimilide and its putative metabolites by capillary electrophoresis

Reliable methods based on capillary electrophoresis (CE) have been develope d for the separation and quantitation of azimilide, an antiarrhythmic drug under development at Procter & Gamble Pharmaceuticals (P&GP). Both capillar y zone electrophoresis (CZE) and micellar electrokinetic capillary chromato graphy (MECC) were employed in the separation of azimilide from its impurit ies, degradants and/or metabolites. Separation of azimilide from NE-11178, F-410, F-1054 and F-1292 was obtained by MECC at pH 9 with 50 mM sodium dod ecyl sulfate (SDS). The separation of azimilide and NE-10171, a key metabol ite of azimilide, was difficult because their structures differ by only a s ingle methyl group. The best separation was achieved under acidic pH condit ions with cetyltriethyl ammonium chloride (CTAC) additive in the buffer. Al l of the CE separations were completed within a substantially shorter time and with better resolution than the corresponding high-performance liquid c hromatography (HPLC) separations. Quantitation was done with azimilide and NE-10171. Calibration curves ranging from 10 to 1000 mu g/ml were obtained with R-2 greater than 0.997 for both azimilide and NE-10171. The back-calcu lated concentrations of the calibration standards and the recoveries of the quality control (QC) samples were within the acceptance range currently us ed for HPLC methods. These results demonstrated the viability of CE as an a lternative technique for drug metabolism studies in support of pharmaceutic al development. (C) 1998 Elsevier Science B.V. All rights reserved.