ISOLATION OF N,N-DIALKYLATED DERIVATIVES OF VALPROYLGLYCINAMIDE FROM DOG PLASMA BY ACTIVE CHARCOAL ADSORPTION AND THEIR QUANTIFICATION BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

A selective assay for quantification of N,N-dimethylvalproylglycinamid e (DM-VGD) and N,N-diethylvalproylglycinamide (DE-VGD) in dog plasma u tilizing reversed-phase high-performance liquid chromatography and UV detection has been developed. These compounds are derivatives of the p otential anticonvulsant drug, valproylglycinamide, which is currently undergoing clinical trials, The method is based on extraction of dog p lasma with activated charcoal, separation of the charcoal pellet and e xtracting it with methanol, evaporation of the solvent and injecting t he reconstituted residue onto the column, The active charcoal adsorpti on method is reliable and reproducible, and it provides a chromatogram free of interfering endogenous plasma compounds. The assay was valida ted and provided a limit of quantification of 2.3 mmol/l for DE-VGD an d 5.3 mmol/l for DM-VGD. Mean recovery of these compounds from plasma averages 75%, This analytical method is suitable for the quantitative determination of DM-VGD and DE-VGD in plasma and it has been applied t o a pharmacokinetic study of these compounds in a dog. (C) 1997 Elsevi er Science B.V.