Determination of valproic acid in human plasma by LC-MS/MS method / 国际检验医学杂志

ABSTRACT

Objective To develop a rapid and sensitive liquid chromatography-tandem mass spectrometric(LC-MS/MS) method for the determination of valproic acid in human plasma.Methods After treating human plasma sample by acetonitrile protein precipitation method,the analytes were separated on a Shimpack VP-ODS analytical column(150 mm×2.0 mm I.D,5 μm) with the mobile phase of methanol and 5 mmol/L ammonium acetate (55∶45,v/v)at a flow rate of 0.4 mL/min.Detection was carried out by adopting the multiple reaction monitoring(MRM) scanning mode in the API3200 triple quadrupole tandem mass spectrometer,electrospray ionization source,negative ion mode,selected monitoring ionic reactions were m/z 142.9→m/z 142.9(valproic acid) and m/z 179.0→m/z 179.0(1-sulfonic acid).Results Valproic acid and internal standard 1-sulfonic acid retention time were 3.03 min and 2.38 min respectively.The plasma valproic acid linear range was 0.800-80.0 μg/mL(r>0.99) with the lower limit of quantitation(LLOQ) 0.800 μg/mL.The intra-and inter-batch relative standard deviations(RSD) were both less than 15%,and the relative errors(RE) were within ±15%.The mean extraction recovery rate was(84.1±2.4)%,and the mean matrix effect factor was(104.3±2.0)%.In the stability study,valproic acid was found to be stable in plasma under various storage conditions.Conclusion This method is suitable for the determination of valproic acid in human plasma and human pharmacokinetic study of valproic acid semisodium sustained release tablet.