Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
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Simultaneous Determination of Valproic Acid and its Toxic Metabolites, 4-ene-VPA and 2,4-diene-VPA in Rat Plasma using a Gas Chromatographic-mass Spectrometric Method

  • Lee, Min-Sun (Integrated Omics Center, Korea Institute of Science and Technology) ;
  • Lee, Young-Joo (College of Pharmacy, Kyung Hee University) ;
  • Chung, Bong-Chul (Integrated Omics Center, Korea Institute of Science and Technology) ;
  • Jung, Byung-Hwa (Integrated Omics Center, Korea Institute of Science and Technology)
  • Received : 2010.04.02
  • Accepted : 2010.05.31
  • Published : 2010.06.20
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Abstract

A gas chromatographic-mass spectrometric (GC-MS) method was developed for the simultaneous determination of valproic acid (VPA) and its toxic metabolites, 4-ene-VPA and 2,4-diene-VPA in rat plasma. Extraction was performed in weak acidic condition (pH 5.2) to avoid degradation of 4-ene-VPA and 2,4-diene-VPA. The recoveries for 4-ene-VPA and 2,4-diene-VPA were more than 70% and that for VPA was 33-42%. R value for each compounds exceeded 0.998 in calibration curve during all the analysis. Accuracy and precision ranged from 88.3 to 113.2% and from 2.16 to 14.2%, respectively The method was successfully applied to monitor plasma concentrations of VPA, 4-ene-VPA and 2,4-diene-VPA after intravenous administration of VPA at the dose of 100 mg/kg, suggesting that these toxic metabolites may involved in the hepatotoxicity induced by VPA.

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References

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