Metabolic profiling of valproic acid in patients using negative-ion chemical ionization gas chromatography-mass spectrometry

Journal of Chromatography
K KassahunF S Abbott

Abstract

A negative-ion chemical ionization gas chromatographic-mass spectrometric method for the determination of valproic acid (VPA) and fourteen of its metabolites in a single chromatographic run is reported. The assay features the use of four internal standards and is applicable to the analysis of small serum and urine volumes. A combination of pentafluorobenzyl and trimethylsilyl derivatization resulted in the [M - 181]- ion as the base peak for all the metabolites measured. When these ions were monitored sensitivities in the low picogram levels were achieved. The VPA metabolite profile was determined in pediatric patients on VPA monotherapy and on combined VPA therapy with either carbamazepine or clobazam. The recently characterized diene metabolite, (E,E)-2,3'-diene-VPA, was found to be a major serum metabolite of VPA. In the patient groups taking VPA in combination with carbamazepine, the induction of omega and omega-1 pathways of VPA metabolism was apparent, while the levels of the beta-oxidation products were significantly decreased.

References

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Aug 1, 1989·Journal of Pharmaceutical Sciences·R D LeeF S Abbott
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Citations

Mar 12, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Daniel F Chollet
Dec 31, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Hans Jörg LeisGünter Fauler
Jun 15, 2005·Rapid Communications in Mass Spectrometry : RCM·N V S RamakrishnaB Ravi Kumar
Jan 1, 2001·Journal of Liposome Research·F J Belas, I A Blair

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