| Autor: |
Tao X; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR 999078, China., Liu JY; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR 999078, China., Zhou JY; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR 999078, China., Dai JK; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR 999078, China., Xiao Z; Collaborative Translational Medicine Collaborative Innovation Center, Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China., Li HK; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Wan JB; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR 999078, China. |
| Abstrakt: |
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. |
