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.
Research Unit of Osteology and Analytical Mass Spectrometry, University Children's Hospital, Medical University Graz, Auenbruggerplatz 30, 8036 Graz, Austria.
Bernhard M
BM
Wagner
Fabrizio
F
Donnarumma
Reinhold
R
Wintersteiger
Werner
W
Windischhofer
Hans J
HJ
Leis
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