OBJECTIVE:To establish a method for simultaneous determination of sodium valproate(VPA)and its metabo-lite 2-propyl-2-pentenoic acid (2-ene-VPA) in human plasma. METHODS:Plasma sample was extracted with cyclohexane and experienced derivatization with 2,4′-dibromoacetophenone using n-octanoic acid as an internal standard. RP-HPLC method was adopted. The determination was performed on Zorbax SB-C18 column with mobile phase consisted of acetonitrile-water(65∶35,V/V)at the flow rate of 1 mL/min. The column temperature was set at 35 ℃,and UV dectection wavelenth was set at 258 nm. The sample size was 20 μL. RESULTS:The linear range of VPA and 2-ene-VPA were 5.0-200.0,0.5-20.0 μg/mL(r=0.999 9, n=5). The limits of quantification were 5.0,0.5 μg/mL. RSDs of inter-day and intra-day were all lower than 5%. Method recov-eries were 95.99%-98.80%and 97.40%-98.17%,and extraction recoveries were 80.46%-86.23%and 80.45%-85.61%. The plas-ma concentrations of VPA in 10 epileptic children were 27.4-93.2 μg/mL,and those of 2-ene-VPA were 0.85-3.94 μg/mL,respec-tively. CONCLUSIONS:The method is simple,specific and suitable for plasma concentration determination and pharmacokinet-ic study of VPA.

Valproic acid is metabolized via β-oxidation in the body and produces 2-propyl-2-pentenoic acid(2-ene-VPA)which has antiepileptic activity and sedation but also has certain hepatotoxicity and neurotoxicity. 2-ene-VPA is eliminated slowly than VPA and has a high binding protein as to VPA. Hepatotoxicity of 2-ene-VPA is lesser than VPA but also can interfere with the normal oxidation of fatty acid. The valproic acid-induced hyperammonemic encephalopathy may refer to the accumulation of 2-ene-VPA in brain. The pharmacological action and safety of 2-ene-VPA need more pre-clinical evaluation.

Valproic acid is metabolized via β-oxidation in the body and produces 2-propyl-2-pentenoic acid(2-ene-VPA)which has antiepileptic activity and sedation but also has certain hepatotoxicity and neurotoxicity. 2-ene-VPA is eliminated slowly than VPA and has a high binding protein as to VPA. Hepatotoxicity of 2-ene-VPA is lesser than VPA but also can interfere with the normal oxidation of fatty acid. The valproic acid-induced hyperammonemic encephalopathy may refer to the accumulation of 2-ene-VPA in brain. The pharmacological action and safety of 2-ene-VPA need more pre-clinical evaluation.