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.