Determination of valproic acid and 3-heptanone in plasma using a microextraction method: Application to the real samples

Introduction: Valproic acid (VPA) is a well-established anticonvulsant drug that has been increasingly used in the treatment of many forms of generalized epilepsy. Although there are many reports of adverse effects of VPA, studies focusing on the concentration–response relationships of VPA and its metabolites in patients with refractory epilepsy are extremely limited. In this paper, a high efficient method was developed for the extraction, preconcentration, and determination of valproic acid and its main metabolite in plasma. Method: For the extraction and preconcentration of the selected analytes, a volume of an extraction solvent was placed at the bottom of the microtube containing pretreated plasma. The mixture was rapidly withdrawn into a 1-mL syringe and then pushed-out into the tube in order to form a cloudy mixture. For the further turbidity, the mixture was shaken on a vortex agitator. Result: This procedure was used to analyze plasma samples of Iran patients with epilepsy (n = 70). The results revealed that in most patient with low level of valproic acid relative to expected level of valproic acid, amount of 3-heptanone was high. The limits of quantification of the valproic acid and 3-heptanone were obtained 0.2 mg L–1 and 0.04 mg L–1, respectively. An acceptable precision was obtained for the concentrations of 2 mg L-1 each analyte (relative standard deviation ≤ 9 %). Conclusion: The obtained results showed that this method is simple, sensitive and reliable and can be used for analysis of the selected analytes in plasma sample of patient with epilepsy.