Gas Chromatographic Analysis of Sodium Valproate in Plasma and Urine after Air Assisted Liquid-Liquid Microextraction

Rapid, highly efficient, and reliable liquid–liquid microextraction (LLME) methods followed by gas chromatography-flame ionization detection were developed for the extraction, preconcentration, and determination of valproate in human plasma and urine samples. Proteins of plasma sample are precipitated by adding methanol and urine sample was diluted prior to performing the microextraction procedures. Fine organic solvent droplets were formed by repeated suction and injection of the mixture of sample solution and extraction solvent into a test tube with a glass syringe. After extraction, phase separation was performed by centrifuging and the enriched analytes in the sedimented organic phase were determined by the separation system. The main factors influencing the extraction efficiency including extraction solvent type and volume, salt addition, pH, and extraction times are investigated. Under the optimized conditions, the proposed method showed good precision (relative standard deviation less than 8%). Limits of detection and lower limits of quantification for valproate were obtained in the ranges of 0.05–0.22 and 0.1–0.5µg mL−1, respectively. The linear ranges were 0.5-500 and 0.1-200 µg mL−1in plasma and urine, respectively (r2 ≥ 0.9995). The relative recoveries varied from 98-102 % and 93-100 %, respectively for plasma and urine samples. The mean relative standard deviations for intra-assay and inter-assay precisions were 3.4 % and 6.0 %, respectively. Preconcentration factors were in the range of 7-44. Good recoveries (55–86%) were obtained for the spiked samples. The proposed method was successfully used to analyze plasma and urine samples of epileptic receiving sodium valproate.