A simple and rapid determination of valproic acid in human plasma using a non-porous silica column and liquid chromatography with tandem mass spectrometric detection

A liquid chromatographic tandem mass spectrometric (LC‐MS/MS) assay was developed and validated to determine valproic acid in human plasma. The method involved a solid‐phase extraction of valproic acid and betamethasone valerate, an internal standard, from plasma and detection using an LC‐MS/MS system with electrospray ionization source in negative ion mode. Separation was achieved within 3 min on a non‐porous silica column with mobile phase containing ammonium acetate and methanol. Multiple reaction monitoring was utilized for detection monitoring at 142.89–142.89 for valproic acid and 457.21–457.21 for the internal standard. The calibration curve for valproic acid was linear over the range of 0.5–150 µg/mL. The limit of detection was 0.17 µg/mL and the lower limit of quantification was 0.5 µg/mL, when 0.2 mL plasma was used for extraction. The percentage coefficient of validation for accuracy and precision (inter‐ and intra‐day) for this method was less than 9.5% with recovery ranging from 82.3 to 86.9% for valproic acid. Copyright © 2007 John Wiley & Sons, Ltd.