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

Dal-Bekar N. E., Tuna G., Islekel S., İşlekel G. H.

BIOANALYSIS, sa.19, ss.1271-1280, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2022
  • Doi Numarası: 10.4155/bio-2022-0168
  • Dergi Adı: BIOANALYSIS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.1271-1280
  • Anahtar Kelimeler: biomarker, D-2-hydroxyglutaric acid, glioma, HPLC, isocitrate dehydrogenase mutation, L-2-hydroxyglutaric acid, stable isotope dilution multiple reaction monitoring, tandem mass spectrometry, TANDEM MASS-SPECTROMETRY, 2-HYDROXYGLUTARATE, MUTATION, ENANTIOMERS, CANCER
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

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.