Simultaneous Quantitation of Alpha-ketoglutaric Acid and 5-Hydroxymethylfurfural in Plasma by HPLC with UV and Fluorescence Detection

Abstract

Alpha-ketoglutaric acid (KG) and hydroxymethylfurfural (HMF) are currently being investigated in clinical trials as an approach in targeted cancer therapy. Hence, a method for the simultaneous determination of KG and HMF in plasma has been developed. Due to the strongly discriminative chemical properties of KG and HMF, SPE purification is performed using an ion-exchange cartridge to separate KG, and a hydrophobic polymeric cartridge to separate HMF. The cartridges are connected together for several steps, thus resulting in a quicker approach for the purification of plasma samples. The derivatization step is based on the reaction of the carbonyl groups of KG and HMF with dansylhydrazine (DNSH) catalyzed by trifluoroacetic acid. The formed derivatives could be separated by reversed-phase LC on a C8-column, and analyzed by UV and fluorescence detection in a single run using a gradient program. The obtained results show good reproducibility, specificity, and detection limits down to the low picomole range.

Cardioprotective effects of 5‐hydroxymethylfurfural mediated by inhibition of L‐type Ca2+ currents

“…One of us (A.O.) has developed an analytical method for quantification of 5‐HMF in plasma (Donnarumma et al, ), and the pharmacokinetics of the compound is currently being studied in clinical trials. In the I/R experiments, 5‐HMF was added before induction of ischaemia, which of course does not reflect the clinical situation of acute myocardial infarction.…”

Alpha-Ketoglutarate as a Molecule with Pleiotropic Activity: Well-Known and Novel Possibilities of Therapeutic Use

“…It should be noted that AKG in combination with 5-hydroxymethylfurfural, prepared in the form of an infusion solution, are currently being investigated for the treatment of patients with non-small-cell lung carcinoma, not responding to any conventional therapy. This combination, named KARAL ® , is currently in phase II clinical study and shows great promises as cancer treatment (Donnarumma et al 2013 ).…”

Simultaneous analysis of 2‐methylimidazole, 4‐methylimidazole, and 5‐hydroxymethylfurfural potentially formed in fermented soy sauce by “quick, easy, cheap, effective, rugged, and safe” purification and UHPLC with tandem mass spectrometry

“…A previous literature reported a vortex‐assisted liquid‐liquid microextraction followed by HPLC–MS/MS method for the detection of 5‐HMF in beverages, and low LOQ (0.3 μg/L), excellent linearity and favorable recoveries were finally obtained . In general, the common column for 2‐MID purification is SCX column , those for 5‐HMF purification comprise Bond Elut ENV column, hydrophobic polymeric column and HLB column . However, strong interaction was generated in C18 and HLB columns in relation to HMF, making it necessary to be eluted by organic solvents.…”