HPLC-MS/ESI Determination of Valproic Acid in Human Serum

Objiective:To establish an HPLC - MS/ESI method to determine valproic acid(VPA) in human serum. The method was utilized in therapeutic drug monitoring (TDM) of valproic acid. Method:Waters XTerra C18 (150 mm×3.9 mm,5μm)column was used with temperature of 45℃. The mobile phase consisted of 10 mmol·L-1 ammonium acetate-acetonitrile (60:40) ,at a flow rate of 0.80 mL·min-1. Diclofene(?) was internal standard. Valproic acid was quantitated by selected ion recording (SIR) with negative ESI. Serum was deposited by acetonitrile directly. Results:The minimal detectable serum drug concentration was 0.50μg·mL-1. The calibration curve was linear in the range of 7.25-188.10μg·mL-1(r=0.9997). The average recovery was between 98.7% and 105.1%. Inter - day and intra - day RSD were less than 10% (n=5). Conclusion:The method is simple, sensitive and accurate. It is suitable for the monitoring of valproic acid concentration in serum.