Isomerization of cannabidiol and Δ9 -tetrahydrocannabinol during positive electrospray ionization. In-source hydrogen/deuterium exchange experiments by flow injection hybrid quadrupole-time-of-flight mass spectrometry

2012 ◽  
Vol 26 (12) ◽  
pp. 1407-1414 ◽  
Author(s):  
Sebastian Broecker ◽  
Fritz Pragst
2019 ◽  
Vol 65 (5) ◽  
pp. 653-663 ◽  
Author(s):  
Jie Chen ◽  
Xueli Li ◽  
Andrew Edmondson ◽  
Gail Ditewig Meyers ◽  
Kosuke Izumi ◽  
...  

Abstract BACKGROUND Congenital disorders of glycosylation (CDG) represent 1 of the largest groups of metabolic disorders with >130 subtypes identified to date. The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides. To improve the diagnostic capability for CDG, we developed and validated a plasma N-glycan assay using flow injection–electrospray ionization–quadrupole time-of-flight mass spectrometry. METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard. RESULTS This assay differed from other N-glycan profiling methods because it was free of any contamination from circulating free glycans and was semiquantitative. The low end of the detection range tested was at 63 nmol/L for disialo-biantennary N-glycan. The majority of N-glycans in normal plasma had <1% abundance. Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis. CONCLUSIONS The clinical specificity and sensitivity of N-glycan analysis was much improved with this method. Additional CDGs can be diagnosed that would be missed by carbohydrate-deficient transferrin analysis. The assay provides novel biomarkers with diagnostic and potentially therapeutic significance.


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