Abstract

A sensitive capillary gas chromatographic-mass spectrometric method for the determination of valproic acid and at least twelve of its metabolites in serum based on tert.-butyldimethylsilyl ( tBDMS) derivatives is described. Low detection limits are achieved by using a direct on-column injection technique. The addition of dry pyridine during the derivatization step now leads to uniform formation of 3-keto-VPA di- tBDMS derivatives and thereby avoids the necessity of a deuterated internal standard. A novel extraction procedure for metabolic profiling of valproate in brain tissue samples is presented. Using this method, (Z)-2-en-VPA was determined in rat brain tissue for the first time.

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