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Type: Journal article
Title: Butanolysis derivatization: improved sensitivity in LC-MS/MS quantitation of heparan sulfate in urine from mucopolysaccharidosis patients
Author: Trim, P.
Hopwood, J.
Snel, M.
Citation: Analytical Chemistry, 2015; 87(18):9243-9250
Publisher: American Chemical Society
Issue Date: 2015
ISSN: 0003-2700
Statement of
Paul J. Trim, John J. Hopwood, and Marten F. Snel
Abstract: Heparan sulfate (HS) is a complex oligosaccharide that is a marker of a number of diseases, most notably several of the mucopolysaccharidoses (MPS). It is a very heterogeneous compound and its quantification at physiological concentrations in patient samples is challenging. Here, we demonstrate novel derivatization chemistry for depolymerization/desulfation and alkylation of HS based on butanolysis. The resultant alkylated disaccharides are quantifiable by LC-MS/MS. This new method is at least 70-fold more sensitive than a previously published methanolysis method. Disaccharide yield over time is compared for methanolysis, ethanolysis, and butanolysis. Maximum disaccharide concentration was observed after 2 h with butanolysis and 18 h with ethanolysis whereas a maximum was not reached over the 24 h of the experiment with methanolysis. The sensitivity of the new technique is illustrated by the quantification of HS in 5 μL urine samples from MPS patients and healthy controls. HS was quantifiable in all samples including controls. Disaccharide reaction products were further characterized using exact mass MS/MS.
Keywords: Humans; Mucopolysaccharidoses; Butanols; Methanol; Heparitin Sulfate; Urinalysis; Chromatography, Liquid; Adolescent; Child; Child, Preschool; Infant; Female; Male; Tandem Mass Spectrometry; Young Adult; Limit of Detection
Rights: © 2015 American Chemical Society
RMID: 0030036205
DOI: 10.1021/acs.analchem.5b01743
Appears in Collections:Medicine publications

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