Numerous bioactive compounds containing carbonyl groups, including aldehydes and ketones, are widely acknowledged as potential biomarkers for several diseases and are implicated in the development of metabolic disorders. However, the detection of carbonyl metabolites is hindered by challenges, such as poor ionization efficiency, low biological concentration, instability, and complexity of the sample matrix. To overcome these limitations, we developed a Girard derivatization-based enrichment (GDBE) strategy for capturing and comprehensively profiling carbonyl metabolites in biological samples. A functionalized resin, named carbonyl capture and reporter-ion installation (CCRI) resins, was synthesized to selectively capture carbonyl metabolites via a Girard reaction. After unwanted metabolites were removed, the hydrazone derivatives were cleaved from the solid-phase resins and subjected to LC-MS analysis. The proposed GDBE strategy exhibits exceptional selectivity for capturing and enriching carbonyl metabolites. Moreover, this method surpasses current detection limits by enhancing the MS sensitivity and facilitating structural characterization of hydrazone derivatives by a specific MS/MS fragmentation signature. Using the GDBE method, 957 potential carbonyl metabolites were successfully identified in liver tissue from alcohol-fed mice. Among them, 76 carbonyl metabolites were annotated, indicating the potential of this strategy for the efficient nontargeted profiling of the carbonyl submetabolome in complex biological samples.

中文翻译：

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基于 Girard 衍生化的富集策略，用于分析生物样品中的羰基亚代谢组


许多含有羰基（包括醛和酮）的生物活性化合物被广泛认为是多种疾病的潜在生物标志物，并与代谢紊乱的发展有关。然而，羰基代谢物的检测受到电离效率差、生物浓度低、样品基质不稳定和复杂性等挑战的阻碍。为了克服这些限制，我们开发了一种基于 Girard 衍生化的富集 （GDBE） 策略，用于捕获和全面分析生物样品中的羰基代谢物。合成了一种名为羰基捕获和报告离子安装 （CCRI） 树脂的功能化树脂，用于通过 Girard 反应选择性捕获羰基代谢物。去除不需要的代谢物后，从固相填料中裂解腙衍生物并进行 LC-MS 分析。所提出的 GDBE 策略在捕获和富集羰基代谢物方面表现出卓越的选择性。此外，该方法通过提高 MS 灵敏度并促进通过特定的 MS/MS 碎裂特征对腙衍生物进行结构表征，超越了当前的检测限。使用 GDBE 方法，在酒精喂养小鼠的肝组织中成功鉴定了 957 种潜在的羰基代谢物。其中，注释了 76 种羰基代谢物，表明该策略在复杂生物样品中对羰基亚代谢组进行有效非靶向分析的潜力。