| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1212822 | Journal of Chromatography B | 2013 | 8 Pages |
•We developed a rapid and highly sensitive UPLC/ESI-MSMS bioanalytical method for the detection of VPA.•Pre-column derivatization with 2-picolylamine was employed to increase the ionization efficiency of VPA in MRM mode.•The utility of this method was demonstrated in in vivo percutaneous pharmacokinetic study of VPA using rats.•This method will be useful for the studies that require a high sensitivity and efficiency.
A rapid, highly sensitive and specific ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC–MS/MS) for the detection of valproic acid (VPA) in rat plasma following the topical application was developed and validated. This method was carried out with pre-column derivatization using 2-picolylamine (PA) which reacts with the carboxylic acid group of VPA. The derivatization was completed in 10 min and the resulting PA-VPA derivative enabled the sensitive detection of VPA in selected reaction monitoring (SRM) mode. Sample preparation was done with simple liquid–liquid extraction and chromatographic separation was achieved within 5 min on a C18 column using a gradient elution with the mobile phase of 2 mM ammonium formate containing 0.1% formic acid and methanol. The standard curves were linear over the concentration range of 0.07–200 μg/mL with a correlation coefficient higher than 0.99. The limit of detection (LOD) and the lower limit of quantification (LLOQ) was 0.03 and 0.07 μg/mL, respectively with 100 μL of plasma sample. The intra- and inter-day precisions were measured to be below 10.7% and accuracies were within the range of 94.1–115.9%. The validated method was successfully applied to the pharmacokinetics of VPA in the rat following topical and intravenous applications.
