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A capillary column gas chromatography--mass fragmentographic method for metapramine and its three major demethylated metabolites is described. Compounds are extracted from plasma using a double-extraction procedure and transformed into N-trifluoroacetyl derivatives. The detection is performed by monitoring specific ions for metapramine and for its metabolites with a mass detector. In spite of extensive metabolism in the liver and rapid elimination of metapramine, plasma concentrations of both metapramine and its metabolites can be simultaneously followed over 24 h after a single 150-mg oral dose, because of the sensitivity and selectivity of the method. This method has been successfully applied to the analysis of samples obtained from patients who were at steady state with metapramine and to a pharmacokinetic study in a healthy volunteer.
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