The prevention of marine biofouling remains a global challenge due to environmental concerns associated with current biocidal antifouling (AF) agents …

Nucleosides and their modified forms serve as fundamental building blocks of nucleic acids and play critical roles in epigenetic regulation, RNA metab…

Journal of the American Society for Mass SpectrometryDOI: 10.1021/jasms.5c00245

Liquid chromatography-tandem mass spectrometry has been widely used to quantify modified nucleosides enzymatically released from RNA and DNA. Compared to MS/MS, MS3 offers higher specificity for analytes in complex sample matrices because coeluting chemical interferences can be more effectively filtered out. To date, the detection of uracil- and thymine-containing nucleosides and their modified derivatives still suffers from poor sensitivity, owing, in part, to their relatively low proton affinities. In this study, we explored various settings of q values in the MS3 analysis of unmodified and chemically modified uridine and thymidine nucleosides on a linear ion trap mass spectrometer. Our results showed that increasing the q value led to markedly improved sensitivities for detecting some of these nucleosides using MS3. Our work suggests that optimizing the q value constitutes a useful approach for the highly sensitive detection of modified nucleosides and other types of analytes by MS3.

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