Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, Karl-Franzens University Graz, Graz, Austria.
J Sep Sci. 2012 Oct;35(19):2567-74. doi: 10.1002/jssc.201200251. Epub 2012 Sep 3.
The food component 5-hydroxymethylfurfural is supposed to have antioxidative properties and is therefore used as an acting agent in a novel anticancer infusion solution, named Karal®, and an oral supplementation. Previous studies showed that after oral and intravenous application, the substance is completely decomposed to its metabolites: 5-hydroxymethylfuroic acid, 2,5-furandicarboxylic acid, and N-(hydroxymethyl)furoyl glycine. The formation of a fourth metabolite, namely 5-sulphoxymethylfurfural, is still not clarified according to literature. Due to commercial unavailability, synthesis of 5-sulphoxymethylfurfural was conducted and a synthesis procedure for N-(hydroxymethyl)furoyl glycine had to be developed. Identification of the synthesised compounds was proven by LC-MS and NMR. An appropriate HPLC method was established to obtain good separation of the four possible metabolic substances and 5-hydroxymethylfurfural within 12 min via a HILIC column (150 × 4.6 mm, 5 μm) using a gradient grade system switching from mobile phase A (ACN/ammonium formate 100 mM, pH 2.35, 95:5, v/v) to mobile phase B (ACN/ammonium formate 100 mM, pH 2.35, 85:15, v/v). The procedure was afterward validated following ICH guidelines in terms of selectivity, linearity, precision, LOD, and LOQ.
食品成分 5-羟甲基糠醛据称具有抗氧化特性，因此被用作一种新型抗癌输液溶液 Karal®和口服补充剂的活性剂。先前的研究表明，口服和静脉注射后，该物质会完全分解为其代谢物：5-羟甲基糠酸、2,5-呋喃二甲酸和 N-(羟甲基)糠酰甘氨酸。根据文献，第四种代谢物 5-磺基甲基糠醛的形成仍不清楚。由于商业上无法获得，因此进行了 5-磺基甲基糠醛的合成，并开发了 N-(羟甲基)糠酰甘氨酸的合成方法。通过 LC-MS 和 NMR 证明了合成化合物的鉴定。建立了适当的 HPLC 方法，通过使用 HILIC 柱（150×4.6mm，5μm）在 12 分钟内通过梯度梯度系统从流动相 A（ACN/甲酸铵 100mM，pH2.35，95:5，v/v）切换到流动相 B（ACN/甲酸铵 100mM，pH2.35，85:15，v/v），可获得四种可能的代谢物质和 5-羟甲基糠醛的良好分离。该方法随后根据 ICH 指南进行了选择性、线性、精密度、LOD 和 LOQ 的验证。
