Quantitative Simultaneous Determination of Eight Common Antiepileptic Drugs and Metabolites by Liquid Chromatography

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Abstract
Specific antiepileptic drug (AED) concentrations in serum are believed to cause therapeutic effects in individual patients. Multiple drug therapy requires simultaneous separation and quantitation of the various drugs and their metabolites. The advantages and disadvantages of current AED analysis methods are discussed. Liquid chromatography (LC) is the most versatile technique for routine and research analysis and can be applied to the determination of common, less common and new AED and metabolites. Carbamazepine and its metabolite, carbamazepine-10,11-epoxide, were determined with high accuracy. The sample preparation procedures, the internal standards, and mode of LC separation used for the analysis are given. The chromatographic parameters for optimized resolution and analysis time of 8 AED and metabolites were devised with special consideration for the influence of the oven temperature on resolution. About 300 patient serum samples were analyzed by automatic unattended operation. By this method 50 samples/day can be extracted and analyzed. Quantitative results achieved by LC and GLC on the same patient samples are reported and chromatograms discussed. Peak scanning was used to demonstrate the presence of compounds which could eventually interfere with the detection of phenylethylmalonamide. The overall accuracy of the employed LC method, the repeatability of retention times on 3 different columns, and the measured ranges of AED concentrations are reported. The drugs and metabolites studied were phenylethylmalondiamide, ethosuximide, primidone, methylpropylsuccinimide, phenobarbital, N-demethyl methsuximide, phenytoin, carbamazepine, carbamazepine 10,11-epoxide and methylphenylphenylhydantoin.