Aim: The study aimed to develop an LC-MS/MS assay to measure dermatan sulfate (DS) in human cerebrospinal fluid (CSF).
Methods & results: DS was quantified by ion pairing LC-MS/MS analysis of the major disaccharides derived from chondroitinase B digestion. Artificial CSF was utilized as a surrogate for calibration curve preparation. The assay was fully validated, with a linear range of 20.0-4000 ng/ml, accuracy within ±20%, and precision of ≤20%. CSF samples from mucopolysaccharidoses (MPS) II patients showed an average of 11-fold increase in DS levels compared with controls.
Conclusion: The described assay is capable of differentiating DS levels in the CSF of MPS II patients from controls and can be used to monitor disease progression and therapeutic responses.
Keywords: cerebrospinal fluid; dermatan sulfate; fit-for-purpose validation; glycosaminoglycans; ion pairing LC–MS/MS; mucopolysaccharidosis II; surrogate matrix.