Modified metabolites mapping by liquid chromatography-high resolution mass spectrometry using full scan/all ion fragmentation/neutral loss acquisition

Abstract Modified metabolites play important roles in diagnostic monitoring, oxidative response and physiological regulation. Comprehensive analytical methods are greatly needed for improving the coverage of modified metabolites and studying their physiological function. Here, a novel nontargeted profiling method for mapping modified metabolites was developed by liquid chromatography-high resolution mass spectrometry with full scan/all ion fragmentation/neutral loss (FS/AIF/NL) data acquisition. Modified metabolites were unbiasedly defined with less false positive results by mixed standards verification. Thirteen types of modified metabolites in urine were analyzed at the same time, and 198 of 307 modified metabolites at positive mode and 166 of 366 modified metabolites at negative mode were putatively identified. The modified metabolites profiling method was applied for investigating the metabolic differences between the patients with breast cancer and health controls. As a result, many modified metabolites with glucuronidation, ribosylation and indole acetylation modification were significantly up-regulated in breast cancer and four modified metabolites including 7-methylguanosine, N 4 -acetylcytidine, dihyroxy-1H-indole glucuronide I and indole-3-acetic acid- O -glucuronide were identified as potential biomarkers for the diagnose of breast cancer.