Abstract
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.
Highlights
Short-chain carboxylic acids, aldehydes and ketones serve important functions in almost all biological processes inside the body, especially in nutrient and energy metabolism
Among many derivatization methods for GC analysis, a tandem oximation-silylation procedure has been widely adopted in practice, in which oximation of aldehydes and ketones is commonly achieved by the reactions between carbonyl group and methoxyamine, while the reactions with silylation agents replace the active hydrogen in alcohols, carboxylic acids, amines and thiols [5,6]
HQ derivatization improved the chromatographic performance and ionization efficiency of short-chain carboxylic acid derivatives, and produced derivatives with various aldehydes and ketones. To further confirm this observation and explore the application of HQ in liquid chromatography-mass spectrometry (LC-MS)-based metabolite profiling and metabolomic analysis, the reactivities of HQ, HP, 2-picolylamine (PA) and dansyl hydrazine (DH) with a mixture of test compounds were compared under a common reaction condition [21]
Summary
Short-chain carboxylic acids, aldehydes and ketones serve important functions in almost all biological processes inside the body, especially in nutrient and energy metabolism. They are substrates and products of numerous enzymatic reactions, intermediate metabolites in both anabolic and catabolic metabolism, building blocks for complex biomolecules, regulators of metabolic pathways and causes of metabolic disorders and oxidative stress. Analyzing these metabolites in biological samples is essential for understanding the mechanisms behind the homeostasis or disruption of a biological system [1,2,3], but can be challenging due to various factors, including the interferences of complex biological matrices, inherent low concentrations in samples and the limitation of analytical methods. The products of oximation-silylation derivatization are more stable and have better chromatographic performance than their precursor metabolites [7]
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