Chalet Clément, Hollebrands Boudewijn, Janssen Hans-Gerd, Augustijns Patrick, Duchateau Guus
Unilever R&D, Olivier van Noortlaan 120, 3133AT, Vlaardingen, The Netherlands.
Drug Delivery and Disposition, KU Leuven, O&N II Herestraat 49, Box 921, 3000, Leuven, Belgium.
Anal Bioanal Chem. 2018 Jan;410(2):471-482. doi: 10.1007/s00216-017-0737-4. Epub 2017 Nov 22.
Flavonoids are a class of natural compounds with a broad range of potentially beneficial health properties. They are subjected to an extensive intestinal phase-II metabolism, i.e., conjugation to glucuronic acid, sulfate, and methyl groups. Flavonoids and their metabolites can interact with drug transporters and thus interfere with drug absorption, causing food-drug interactions. The site of metabolism plays a key role in the activity, but the identification of the various metabolites remains a challenge. Here, we developed an analytical method to identify the phase-II metabolites of structurally similar flavonoids. We used liquid chromatography-ion-mobility spectrometry-mass spectrometry (LC-IMS-MS) analysis to identify phase-II metabolites of flavonols, flavones, and catechins produced by HT29 cells. We showed that IMS could bring valuable structural information on the different positional isomers of the flavonols and flavones. The position of the glucuronide moiety had a strong influence on the collision cross section (CCS) of the metabolites, with only minor contribution of hydroxyl and methyl moieties. For the catechins, fragmentation data obtained from MS/MS analysis appeared more useful than IMS to determine the structure of the metabolites, mostly due to the high number of metabolites formed. Nevertheless, CCS information as a molecular fingerprint proved to be useful to identify peaks from complex mixtures. LC-IMS-MS thus appears as a valuable tool for the identification of phase-II metabolites of flavonoids. Graphical abstract Structural identification of phase-II metabolites of flavonoids using LC-IMS-MS.
黄酮类化合物是一类具有广泛潜在有益健康特性的天然化合物。它们会经历广泛的肠道Ⅱ相代谢，即与葡萄糖醛酸、硫酸盐和甲基结合。黄酮类化合物及其代谢产物可与药物转运体相互作用，从而干扰药物吸收，导致食物-药物相互作用。代谢部位在活性中起关键作用，但鉴定各种代谢产物仍然是一项挑战。在此，我们开发了一种分析方法来鉴定结构相似的黄酮类化合物的Ⅱ相代谢产物。我们使用液相色谱-离子淌度质谱联用（LC-IMS-MS）分析来鉴定HT29细胞产生的黄酮醇、黄酮和儿茶素的Ⅱ相代谢产物。我们表明，离子淌度质谱（IMS）可以为黄酮醇和黄酮的不同位置异构体带来有价值的结构信息。葡萄糖醛酸部分的位置对代谢产物的碰撞截面（CCS）有很大影响，而羟基和甲基部分的贡献较小。对于儿茶素，从串联质谱（MS/MS）分析获得的碎片数据在确定代谢产物结构方面似乎比离子淌度质谱更有用，这主要是因为形成的代谢产物数量众多。然而，作为分子指纹的CCS信息被证明有助于从复杂混合物中识别峰。因此，LC-IMS-MS似乎是鉴定黄酮类化合物Ⅱ相代谢产物的有价值工具。图形摘要 使用LC-IMS-MS对黄酮类化合物Ⅱ相代谢产物进行结构鉴定。
