Simultaneous Gas Chromatographic Determination of Trimethadione and Dimethadione in Human Plasma

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Abstract
A gas chromatographic assay for the simultaneous determination of the antiepileptic agent trimethadione (TMO (3,5,5-trimethoxyloxazolidine-2,4-dione)) and its metabolite, dimethadione (DMO), in human plasma is described. An organic solvent extraction system was devised to provide adequate recoveries of TMO (.apprx. 100%) and DMO (74%) and to eliminate the need of adding dry inorganic salts to salt out the very hydrophilic metabolite, DMO. Solvent evaporation steps were eliminated from the extraction method to avoid nonreproducible losses of TMO and DMO. The use of double internal standards, paramethadione and .alpha.,.alpha.,.beta.-trimethylsuccinimide, for quantitations of TMO and DMO, respectively, increased the precision and accuracy of the assay.

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