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.
Darius, J. (1996). On-column gas chromatographic-mass spectrometric assay for metabolic profiling of valproate in brain tissue and serum. Journal of Chromatography B: Biomedical Applications, 682(1), 67–72. https://doi.org/10.1016/0378-4347(95)00559-5