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KMID : 0369820100400030155
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Jorunal of Korean Pharmaceutical Sciences
2010 Volume.40 No. 3 p.155 ~ p.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
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Lee Min-Sun
Lee Young-Joo
Chung Bong-Chul
Jung Byung-Hwa
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Abstract
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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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KEYWORD
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valproic acid (VPA), 4-ene-VPA, 2, 4-diene-VPA, quantitative analysis, GC-MS (gas chromatographic-mass spectrometry), pharmacokinetics
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