Simultaneous Gas Chromatographic Determination of Trimethadione and Dimethadione in Human Plasma

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A gas chromatographic assay for the simultaneous determination of trimethadione (TMO) and its metabolite, dimethadione (DMO), in human plasma is described. An organic solvent extraction system has been devised to provide adequate recoveries of TMO (~100%) and DMO (74%) and to eliminate the need of adding dry inorganic salts in order to “salt out” the very hydrophilic metabolite, DMO. Solvent evaporation steps have been eliminated from the ex-traction method in order to avoid nonreproducible losses of TMO and DMO. The use of double internal standards, paramethadione and α, α, β-trimethylsuccinimide, for quantitations of TMO and DMO, respectively, increased the precision and accuracy of the assay.

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