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Development of a LC-MS/MS Method For Determination of 4-ene-VPA in Human Plasma

Valproic acid (VPA) is commonly used for the treatment of epilepsy and biopolar disorders, either on its own or in combination with other treatments. The concern with the use of VPA is the close link it has with rare but serious hepatotoxicity [1]. The ‘ene’ metabolites are of particular interest as they are structurally similar to 4-pentenoic acid and hypoglycin which are known hepatic toxicants [2-4]. One of the minor metabolites, (±)-2-Propyl-4-Pentenoic Acid (4-ene-VPA), is of particular interest as it has been identified to have the most significant contribution to liver damage therefore it is critical to get a better understanding of its pharmacology [2, 5-6]. Current publications report a lower limit of quantifications (LLOQ) as low as 20.0 ng/mL with extraction techniques that include derivatisation and solid phase extraction using an analogue internal standard [4, 7, 8].

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