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Journal of pharmaceutical investigation v.40 no.3, 2010년, pp.155 - 160  
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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  );
  • 초록

    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.


  • 주제어

    valproic acid (VPA) .   4-ene-VPA .   2,4-diene-VPA .   quantitative analysis .   GC-MS (gas chromatographic-mass spectrometry) .   pharmacokinetics.  

  • 참고문헌 (13)

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    11. Yu, D., Gordon, J.D., Zheng, J., Panesar, S.K., Riggs, K.W., Rurak D.W., Abott, F.S., 1995. Determination of valproic acid and its metabolites using gas chromatography with mass selective detection: application to serum and urine samples from sheep, J. Chromatogr. B. 666, 269-281. 
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