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Valproic acid (VPA) is an antiepileptic drug used to treat epilepsy and bipolar disorder. Adverse effects of VPA were studied in many reports, however, a dose-response relationship between VPA and its metabolites in epilepsy patients are extremely limited. In this paper, a high efficient method was developed for the preconcentration and determination of VPA and its main metabolite in plasma.  Methods:  For the extraction and preconcentration of the selected analytes, a volume of an extractant was placed at the bottom of the microtube containing pretreated plasma. The mixture was repeatedly withdrawn from the microtube and pushed-out into it using a 1.0-mL glass syringe and resulted in a cloudy mixture. For further turbidity, the mixture was shaken on a vortex agitator. This procedure was used to analyze the plasma samples of patients with epilepsy (n = 70).  Results:  The results revealed that in most patients with a low level of VPA relative to its expected level, 3-heptanone concentrations were high. The limits of quantification of 3-heptanone and VPA were 0.04 mg L -1 and 0.2 mg L -1 , respectively. A suitable precision at a concentration of 2 mg L -1 for each analyte was obtained (relative standard deviation ≤ 9%).  Conclusion:  The obtained results indicated that this procedure is easy, sensitive, and reliable, and can be used for the analysis of the selected analytes in the plasma samples of patients with epilepsy.

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Determination of valproic acid and 3-heptanone in plasma using air-assisted liquid-liquid microextraction with the assistance of vortex: Application in the real samples