title: Determination of valproic acid in human plasma using dispersive liquid-liquid microextraction followed by gas chromatography-flame ionization detection.
abstract: OBJECTIVE
  Dispersive liquid-liquid microextraction coupled with gas chromatography (GC)-flame ionization detector was developed for the determination of valproic acid (VPA) in human plasma.
  
  
  METHODS
  Using a syringe, a mixture of suitable extraction solvent (40 µl chloroform) and disperser (1 ml acetone) was quickly added to 10 ml of diluted plasma sample containing VPA (pH, 1.0; concentration of NaCl, 4% (w/v)), resulting in a cloudy solution. After centrifugation (6000 rpm for 6 min), an aliquot (1 µl) of the sedimented organic phase was removed using a 1-µl GC microsyringe and injected into the GC system for analysis. One variable at a time optimization method was used to study various parameters affecting the extraction efficiency of target analyte. Then, the developed method was fully validated for its accuracy, precision, recovery, stability, and robustness.
  
  
  RESULTS
  Under the optimum extraction conditions, good linearity range was obtained for the calibration graph, with correlation coefficient higher than 0.998. Limit of detection and lower limit of quantitation were 3.2 and 6 μg/ml, respectively. The relative standard deviations of intra and inter-day analysis of examined compound were less than 11.5%. The relative recoveries were found in the range of 97 to 107.5%. Finally, the validated method was successfully applied to the analysis of VPA in patient sample.
  
  
  CONCLUSIONS
  The presented method has acceptable levels of precision, accuracy and relative recovery and could be used for therapeutic drug monitoring of VPA in human plasma.
authors.affiliation: Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Analytical Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran.
authors.forename: Rana
authors.initials: R
authors.lastname: Fazeli-Bakhtiyari
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Panahi-Azar
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Sorouraddin
authors.affiliation: Pharmaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Abolghasem
authors.initials: A
authors.lastname: Jouyban
keywords: Dispersive liquid-liquid microextraction; Gas chromatography-flame ionization detector; Human plasma; Valproic acid