%0 Journal Article
%T Quantitation of 2-hydroxyglutarate in human plasma via LC-MS/MS using a surrogate analyte approach.
%A Yin F
%A Ling Y
%A Keller J
%A Kraus D
%A Narayanaswamy R
%A Mangus H
%A Li F
%A Yang H
%A Liu G
%J Bioanalysis
%V 12
%N 16
%D Aug 2020
%M 32757862
%F 2.695
%R 10.4155/bio-2020-0131
%X Aim: 2-Hydroxyglutarate (2-HG) is a target engagement biomarker in patients after treatment with inhibitors of mutated isocitrate dehydrogenase (mIDH). Accurate measurement of 2-HG is critical for monitoring the inhibition effectiveness of the inhibitors. Materials & methods: Human plasma samples were spiked with stable isotope labelled internal standard, processed by protein precipitation, and analyzed using LC-MS/MS. This method was validated following regulatory guidance and has been successfully applied in a clinical study for mIDH inhibition. Results: An LC-MS/MS method with a surrogate analyte approach was developed and validated to measure 2-HG in human plasma with acceptable intra- and inter-assay accuracy and precision. Conclusion: A sensitive and robust LC-MS/MS method was developed and validated for measuring 2-HG in human plasma.