67244-24-0Relevant academic research and scientific papers
Metabolite pattern of valproic acid. I. Gaschromatographic determination of the valproic acid metabolite artifacts, heptanone-3, 4- and 5-hydroxyvalproic acid lactone
Schaefer,Luehrs
, p. 657 - 662,658,660 (2007/10/05)
Metabolites arising from enzymatic oxidation of valproic acid (VPA, Orfiril) are determined after incubating body fluids at 37°C with an equal volume of diluted mineral acid, such as 85% w/w H3PO4/1 N HCl (1 : 1, v/v) for 3 h. 3-Ketovalproic acid (3-keto-VPA, 2-propyl-3-ketovaleric acid), which appears as the main metabolite, is hereby converted into heptanone-3 by ketonic hydrolysis. 4-Hydroxyvalproic acid (4-hydroxy-VPA, 2-propyl-4-hydroxyvaleric acid) and 5-hydroxyvalproic acid (5-hydroxy-VPA, 2-propyl-5-hydroxyvaleric acid) are converted into their corresponding lactones (4-HVL, 5-HVL). The kinetics of these reactions was studied using synthesized reference substances. Ketonic hydrolysis and lactone formation under the conditions for extraction procedures were reproducible and almost quantitative. An accurate and rapid determination of these metabolites as well as VPA from body fluids, if necessary after treating with glucuronidase, is thus made possible. A preliminary study of the metabolite patterns of patients on VPA therapy is presented. 3-Keto-VPA, 4-hydroxy-VPA and 5-hydroxy-VPA are excreted predominantly as the non-conjugates. 4-Hydroxy-VPA is also occasionally detected in the serum in quantities of 1-2 μg/ml.
