title: Five doubly unsaturated metabolites of valproic acid in urine and plasma of patients on valproic acid therapy.
abstract: The urine and plasma of epileptic patients receiving therapeutic doses of valproic acid (2-propyl- pentanoic acid) was found to contain five doubly unsaturated metabolites of valproic acid, which were identified as their trimethylsilyl derivatives by GC/MS. A series of reference substances was synthesized but only two of them were identical with native metabolites: 2(2-propenyl)-4-pentenoic acid (= 4.4'-diene) and E-2-propyl-2.4- pentadienoic acid (E-2.4-diene). The mass-spectra of the five native metabolites are given. Preliminary quantitative data obtained from four groups of patients indicate increased formation of doubly unsaturated metabolites when valproic acid-induced side-effects are present, and in cases of fatal hepatic failure. The 4.4'-diene has hitherto been found only in fatal cases with hepatic injury. Quantitative data are presented as % of the sum of valproic acid plus all its detected metabolites.
mesh_terms: D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D005231:Fatty Acids, Unsaturated / Q000097:blood* / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D014635:Valproic Acid / Q000097:blood* / Q000627:therapeutic use / Q000652:urine
chemical_list: D005231:Fatty Acids, Unsaturated; D014635:Valproic Acid