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Abstract
A new mass spectrometry workflow has been developed using the intelligent fragmentation of O-glycans via consecutive reaction monitoring. Using the intensity of selected fragment ions compared to glycan standards, we are able to increase both sensitivity and accuracy of quantification. Furthermore, by taking an intelligent fragmentation strategy we are able to identify and quantify changes in isobaric glycan structures between samples. The limit of detection and linearity of response for quantification of this method has been examined using serial dilutions of O-glycans recovered from a standard sample, mouse brains. This method has been successfully applied to distinguish dystroglycanopathy white blood cell samples from normal phenotype samples. Given that the current diagnosis for congenital muscular dystrophies relies on an invasive muscle biopsy, the development of a diagnostic blood test paves the way for following efficacy in therapeutic trials aimed at improving O-mannosylation in a non-intrusive and sensitive manner.