SIMULTANEOUS DETERMINATION OF FELBAMATE, PRIMIDONE, PHENOBARBITAL, CARBAMAZEPINE, 2 CARBAMAZEPINE METABOLITES, PHENYTOIN, AND ONE PHENYTOINMETABOLITE IN HUMAN PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

An isocratic liquid-chromatographic method employing one extraction st ep has been developed for the quantitation of five drugs and three met abolites in human plasma. The method uses 0.100-ml aliquots of human p lasma and two internal standards. Chromatographic conditions include a 4.6 mm x 150 mm Spherisorb ODS2, 3 mu m a high-performance liquid chr omatography, (HPLC) column, a phosphate buffer-acetonitrile-methanol ( 700:160:140) mobile phase, and ultraviolet (UV) absorbance detection a t 210 nm. Analytes and linear quantitation ranges (mu g/ml) were felba mate (FBM) 0.398-200; primidone (PRIM), 0.09-100; phenobarbital (PHENO ), 0.195-100; carbamazepine (CBZ), 0.195-100; phenytoin (PHT), 0.195-2 00. For CBZ-transdiol (CBZ-TR) CBZ-epoxide (CBZ-EP), and the PHT metab olite, 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), the range was 0.0 49-25.0 mu g/ml. Ethosuximide, methsuximide, 2-methyl-2-phenyl-succini mide (methsuximide metabolite), 2-ethyl-2-phenyl malonamide (PRIM meta bolite, 5-ethyl-5-(4-hydroxyphenyl)-barbituric acid (PHENO metabolite) , and mephenytoin do not interfere with quantitation of the above comp ounds.