Investigators have shown that one enantiomer of hydroxyglutarate (D-2-HG) is abnormally accumulated in a variety of human cancers, such as glioblastoma, acute myeloid leukemia and cholangiocarcinoma. The isocitrate dehydrogenase (IDH) enzyme normally catalyzes the conversion of isocitrate to alpha-ketoglutarate (α-KG), but in these types of cancer, mutant IDH enzymes acquire an abnormal enzymatic activity which allows them to convert α-KG into D-2-HG. The measurement of D-2-HG levels can be used to monitor tumor burden and effectiveness of cancer treatments meant to inhibit mutant IDH.
We have developed and validated a chiral assay for D-2-HG that allows us to accurately quantify levels of this analyte from plasma samples. This assay employs a surrogate matrix in order to quantify absolute levels in the plasma samples. Because D-2-HG is a very small analyte, derivatization was required in order to separate the enantiomers as well as to increase ionization to achieve the desired lower limit of quantitation.
About the Presenter
Dr. Jennifer Zimmer is the Laboratory Director at Alturas Analytics, Inc. and has been working in the field of bioanalysis for over 20 years. She received her B.A. degree in English and Zoology from the University of Idaho and her Ph.D. in Pharmacology from the University of Colorado Health Sciences Center, working in Dr. Robert Murphy’s laboratory on the leukotriene lipid mediator pathway. Her post-doctoral experience in Dr. Richard Smith’s laboratory focused on using metabolomics to elucidate disease pathways and to discover novel biomarker targets.
Dr. Zimmer is responsible for the overall operation of the Alturas Analytics laboratory. She has experience with FTICR, TOF, ion trap and quadrupole instrumentation. She has utilized these instruments for quantitation as well as structure elucidation using HPLC-MS/MS and HPLC-MSn. She oversees the scientific staff and ensures that client deliverables are met while working laterally with the Alturas Analytics, Inc. QAU in order to maintain laboratory compliance with all procedures and regulations. Dr. Zimmer is an active participant the Global CRO Council (GCC) and a member of the American Society for Mass Spectrometry.