On-column gas chromatographic-mass spectrometric assay for metabolic profiling of valproate in brain tissue and serum.
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
J
Department of Clinical Pharmacology, University Hospital, Magdeburg, Germany.
D000081:Acetamides; D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002138:Calibration; D005463:Fluoroacetates; D006801:Humans; D017646:Organosilicon Compounds / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D051381:Rats; D015203:Reproducibility of Results; D014269:Trifluoroacetic Acid / Q000737:chemistry; D014635:Valproic Acid / Q000097:blood / Q000737:chemistry / Q000378:metabolism*
D000081:Acetamides; D000927:Anticonvulsants; D005463:Fluoroacetates; D017646:Organosilicon Compounds; D011725:Pyridines; D014635:Valproic Acid; C059151:N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide; D014269:Trifluoroacetic Acid