A rapid and highly sensitive UPLC-MS/MS method using pre-column derivatization with 2-picolylamine for intravenous and percutaneous pharmacokinetics of valproic acid in rats

Kyung Mi Joo, Dalwoong Choi, Yang Hui Park, Chang Geun Yi, Hye Jin Jeong, Jun Cheol Cho, Kyung Min Lim

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)35-42
Number of pages8
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume938
DOIs
Publication statusPublished - 2013

Keywords

  • 2-Picolylamine
  • Derivatization
  • Pharmacokinetics
  • Topical application
  • UPLC-MS/MS
  • Valproic acid

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

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