Simultaneous quantitative determination of alpha-ketoglutaric acid and 5-hydroxymethylfurfural in human plasma by gas chromatography-mass spectrometry.
Alpha-ketoglutaric acid (alpha-KG) and 5-hydroxymethylfurfural (5-HMF) are currently under investigation as promising cancer cell damaging agents. A method for the simultaneous quantitative determination of alpha-KG and 5-HMF in human plasma was established for screening these compounds in human plasma. Plasma samples were directly treated with O-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine hydrochloride to form the corresponding oximes, thus facilitating subsequent liquid-liquid extraction. After formation of the trimethylsilyl ethers, samples were analyzed by gas chromatography with electron ionization mass spectrometry. Stable isotope labeled standards were used, the preparation of (13)C(6)-5-HMF is described. Limits of quantitation were set to 0.938 microg/mL for alpha-KG and 0.156 microg/mL for 5-HMF. Inter-day accuracy was < or = 93.7% (alpha-KG) and < or = 92.8% (5-HMF). Inter-day precision was < or = 6.0% (alpha-KG) and < or = 4.6% (5-HMF). The method has been successfully applied to pharmacokinetic profiling of the compounds after intravenous application.
Wagner
Bernhard M
BM
Research Unit of Osteology and Analytical Mass Spectrometry, University Children's Hospital, Medical University Graz, Auenbruggerplatz 30, 8036 Graz, Austria.
Donnarumma
Fabrizio
F
Wintersteiger
Reinhold
R
Windischhofer
Werner
W
Leis
Hans J
HJ
D000970:Antineoplastic Agents / Q000097:blood; D001774:Blood Chemical Analysis / Q000379:methods*; D045424:Complex Mixtures / Q000032:analysis; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000097:blood; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D007656:Ketoglutaric Acids / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000970:Antineoplastic Agents; D045424:Complex Mixtures; D007656:Ketoglutaric Acids; C008046:5-hydroxymethylfurfural; D005662:Furaldehyde