Journal article

Using high-resolution Twin-Ion Metabolite Extraction (HiTIME) mass spectrometry with stable isotope labelling to investigate the metabolism of valproic acid in vivo

Michael G Leeming, Noel Cranswick, Christine E Wright, James Ziogas, Terence J O'Brien, William A Donald, Richard AJ O'Hair



Valproic acid (VPA) is a medication that is widely used in the treatment of epilepsy and bipolar disorder, despite a known potential for liver damage in some patients and a specific risk of teratogenic effects if taken by pregnant women. Here the metabolism of VPA has been investigated in male adult Sprague-Dawley rats using the twin-ion method and HiTIME (High-resolution Twin-Ion Metabolite Extraction) analysis under acute dosing. VPA and 13C4-VPA were administered to rats via intra venous infusion and then blood extracts were analysed by liquid chromatography mass spectrometry (LC-MS). Following HiTIME analysis, 13 high-scoring data regions were identified that were not present in control ..

View full abstract


Funding Acknowledgements

We thank the University of Melbourne Interdisciplinary Seed Grant program for funding. MGL thanks the Elizabeth and Vernon Puzey foundation for a PhD scholarship and The University of Melbourne Faculty of Science of the award of the Norma Hilda Schuster scholarship. We thank Andrew P. Isaac and Bernard J. Pope from Victorian Life Sciences Computation Initiative (VLSCI) for developing the HiTIME program. We gratefully acknowledge Linda Cornthwaite-Duncan for performing rat surgeries, drug administration and blood sampling.