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RNA modifications have been revealed to be essential in many biological activities, and their disorders are associated with various human diseases, including cancers. 2'-O-methyladenosine (A m ), N 1 -methyladenosine (m 1 A), N 6 -methyladenosine (m 6 A), N 6 ,2'-O-dimethyladenosine (m 6 A m ) and N 6 ,N 6 -dimethyladenosine (m 6 2 A) are important adenosine (A) modifications. The noninvasive collection of urine samples and the diverse contents of metabolites in plasma make them favored biofluids for biomarkers discovery. In this work, we established a hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method to quantify these six nucleosides in urine and plasma of healthy controls and breast cancer (BC) patients. The limit of detection (LOD) for A, A m , m 1 A, m 6 A, m 6 A m , and m 6 2 A were 0.0025, 0.01, 0.05, 0.005, 0.005, and 0.005 nM. The results showed that the concentrations of A m , m 6 A, and m 6 A m were increased, whereas m 1 A was decreased in the urine of BC patients compared with the healthy controls. We also found that the level ratios of m 1 A/A, m 6 /A were all reduced in plasma from BC patients, compared with healthy controls. Interestingly, these ratios of methylated adenosine nucleosides to adenosine in plasma could better discriminate BC patients from healthy controls, compared to the levels of these nucleosides. The present study not only suggests these modified adenosines can act as noninvasive biomarkers of BC but also will contribute to investigating the impacts of RNA methylation on the occurrence and development of BC.6 A m /A were all reduced in plasma from BC patients, compared with healthy controls. Interestingly, these ratios of methylated adenosine nucleosides to adenosine in plasma could better discriminate BC patients from healthy controls, compared to the levels of these nucleosides. The present study not only suggests these modified adenosines can act as noninvasive biomarkers of BC but also will contribute to investigating the impacts of RNA methylation on the occurrence and development of BC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)