2-Hydrazinoquinoline as a Derivatization Agent for LC-MS-Based Metabolomic Investigation of Diabetic Ketoacidosis.
2-Hydrazinoquinoline as a Derivatization Agent for LC-MS-Based Metabolomic Investigation of Diabetic Ketoacidosis.
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DOI：
10.3390/metabo3040993
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发表时间：
2013-10-31
期刊：
影响因子：
4.1
通讯作者：
Chen C
中科院分区：
文献类型：
--
作者：
Lu Y;Yao D;Chen C
短链羧酸、醛和酮是许多重要代谢途径的产物和调节剂。它们在生物液体和组织中的水平反映了特定代谢反应的状态、整个代谢系统的稳态和生物实体的健康。在这项研究中，使用2-肼基喹啉（HQ）作为一种新的衍生化试剂进行了探索和优化的同时液相色谱-质谱（LC-MS）分析生物样品中的羧酸，醛和酮。羧酸衍生物的形成归因于HQ和羧基之间的酯化反应，而醛和酮衍生物的产生是通过HQ和羰基之间形成席夫碱。通过衍生尿液、血清和肝脏提取物样品证明HQ与生物样品的相容性。使用这种基于HQ的方法，1型糖尿病诱导的代谢变化的动力学特征在于基于LC-MS的代谢组学分析的尿样品从链脲佐菌素（STZ）治疗的小鼠。随后，羧酸，醛和酮代谢产物与STZ引起的营养和能量代谢的破坏，方便地确定和阐明。总体而言，羧酸、醛和酮的HQ衍生化可作为内源性代谢的基于LC-MS的代谢组学研究的有用工具。
Short-chain carboxylic acids, aldehydes and ketones are products and regulators of many important metabolic pathways. Their levels in biofluids and tissues reflect the status of specific metabolic reactions, the homeostasis of the whole metabolic system and the wellbeing of a biological entity. In this study, the use of 2-hydrazinoquinoline (HQ) as a novel derivatization agent was explored and optimized for simultaneous liquid chromatography-mass spectrometry (LC-MS) analysis of carboxylic acids, aldehydes and ketones in biological samples. The formation of carboxylic acid derivative is attributed to the esterification reaction between HQ and a carboxyl group, while the production of aldehyde and ketone derivatives is through the formation of Schiff bases between HQ and a carbonyl group. The compatibility of HQ with biological samples was demonstrated by derivatizing urine, serum and liver extract samples. Using this HQ-based approach, the kinetics of type 1 diabetes-induced metabolic changes was characterized by the LC-MS-based metabolomic analysis of urine samples from streptozotocin (STZ)-treated mice. Subsequently, carboxylic acid, aldehyde and ketone metabolites associated with STZ-elicited disruption of nutrient and energy metabolism were conveniently identified and elucidated. Overall, HQ derivatization of carboxylic acids, aldehydes and ketones could serve as a useful tool for the LC-MS-based metabolomic investigation of endogenous metabolism.