Development and validation of an LC–MS/MS method for D- and L-2-hydroxyglutaric acid measurement in cerebrospinal fluid, urine and plasma: application to glioma: supplementary data

Aim: IDH mutations have been identified as frequent molecular lesions in several tumor types, particularly
in gliomas. As a putative marker of IDH mutations, elevated D-2-HG has been reported in glioma, acute
myeloid leukemia and intrahepatic cholangiocarcinoma. Excessive production of L-2-HG has also been
described in renal cell carcinoma and 2-hydroxyaciduria. Materials & methods: The authors present a fully
optimized stable isotope dilution multiple reaction monitoring method for quantification of D-/L-2-HG
using LC–MS/MS. This is the first method validation study performed on cerebrospinal fluid, plasma and
urine demonstrating clinical applicability with samples from glioma patients. Results & conclusion: This
method validation study showed high accuracy and precision with low limit of detection and limit of
quantification values. The authors believe that the presented approach is highly applicable for basic and
clinical research on related pathologies.