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2-Hydrazinoquinoline as a Derivatization Agent for LC-MS-Based Metabolomic Investigation of Diabetic Ketoacidosis

机译:2-羟基喹啉作为衍生化剂用于基于LC-MS的糖尿病酮症酸中毒代谢组学研究

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摘要

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.
机译:短链羧酸,醛和酮是许多重要代谢途径的产物和调节剂。它们在生物流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以及生物实体的健康。在这项研究中,探索并优化了使用2-肼基喹啉(HQ)作为新型衍生剂,用于同时液相色谱-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和羰基之间的席夫碱的形成。通过衍生化尿液,血清和肝提取物样品证明了总部与生物样品的相容性。使用这种基于HQ的方法,通过对基于链脲佐菌素(STZ)处理的小鼠的尿液样品进行基于LC-MS的代谢组学分析,可以表征1型糖尿病诱发的代谢变化的动力学。随后,方便地鉴定和阐明了与STZ引起的营养物质破坏和能量代谢相关的羧酸,醛和酮代谢物。总体而言,羧酸,醛和酮的HQ衍生化可作为基于LC-MS的内源代谢代谢组学研究的有用工具。

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