Research Unit of Osteology and Analytical Mass Spectrometry, University Children's Hospital, Medical University Graz, Auenbruggerplatz 30, 8036 Graz, Austria.
Anal Bioanal Chem. 2010 Apr;396(7):2629-37. doi: 10.1007/s00216-010-3479-0. Epub 2010 Feb 14.
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.
α-酮戊二酸（α-KG）和 5-羟甲基糠醛（5-HMF）目前正在作为有前途的癌细胞损伤剂进行研究。建立了一种同时定量测定人血浆中α-KG 和 5-HMF 的方法，用于筛选人血浆中的这些化合物。血浆样品直接用 O-(2,3,4,5,6-五氟苄基)羟胺盐酸盐处理，形成相应的肟，从而便于随后的液-液萃取。形成三甲基硅醚后，用气相色谱-电子电离质谱法进行分析。使用稳定同位素标记的标准品，描述了（13）C（6）-5-HMF 的制备。α-KG 的定量限设定为 0.938μg/mL，5-HMF 的定量限设定为 0.156μg/mL。日内准确度<或=93.7%（α-KG）和<或=92.8%（5-HMF）。日内精密度<或=6.0%（α-KG）和<或=4.6%（5-HMF）。该方法已成功应用于静脉应用后化合物的药代动力学分析。
