Hydrophilic interaction chromatography-multiple reaction monitoring mass spectrometry method for basic building block analysis of low molecular weight heparins prepared through nitrous acid depolymerization

Sun, Xiaojun; Guo, Zhimou; Yu, Miao; Lin, Chi‐Feng; Sheng, Anran; Wang, Zhiyu; Linhardt, Robert J.

doi:10.1016/j.chroma.2016.11.061

Cited by 29 publications

(12 citation statements)

References 22 publications

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“…In fact, heparin/LMWH structural elucidation cannot be performed using a single method but requires the combination of different orthogonal methods, in particularly high-resolution NMR and mass spectrometry (MS) [7,10,11,12]. Particularly, high-resolution MS allowed the achievement of previously unthinkable sensitivity and specificity in identification of heparin-related oligosaccharides and their building blocks [11,12,13,14,15,16]. To overcome the problem of high molecular weight and microheterogeneity, enzymatic degradation with heparinases followed by a refined LC-MS analysis is often involved in the structural characterization scheme [10,17,18,19,20].…”

Section: Introductionmentioning

confidence: 99%

Heparanase as an Additional Tool for Detecting Structural Peculiarities of Heparin Oligosaccharides

et al. 2019

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Due to the biological properties of heparin and low-molecular-weight heparin (LMWH), continuous advances in elucidation of their microheterogeneous structure and discovery of novel structural peculiarities are crucial. Effective strategies for monitoring manufacturing processes and assessment of more restrictive specifications, as imposed by the current regulatory agencies, need to be developed. Hereby, we apply an efficient heparanase-based strategy to assert the structure of two major isomeric octasaccharides of dalteparin and investigate the tetrasaccharides arising from antithrombin binding region (ATBR) of bovine mucosal heparin. Heparanase, especially when combined with other sample preparation methods (e.g., size exclusion, affinity chromatography, heparinase depolymerization), was shown to be a powerful tool providing relevant information about heparin structural peculiarities. The applied approach provided direct evidence that oligomers bearing glucuronic acid–glucosamine-3-O-sulfate at their nonreducing end represent an important structural signature of dalteparin. When extended to ATBR-related tetramers of bovine heparin, the heparanase-based approach allowed for elucidation of the structure of minor sequences that have not been reported yet. The obtained results are of high importance in the view of the growing interest of regulatory agencies and manufacturers in the development of low-molecular-weight heparin generics as well as bovine heparin as alternative source.

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Section: Introductionmentioning

confidence: 99%

Heparanase as an Additional Tool for Detecting Structural Peculiarities of Heparin Oligosaccharides

et al. 2019

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“…Enoxaparin, dalteparin, and other versions of the LWMH drugs are produced through different depolymerization procedures. These heterogeneous mixtures range from dp2 to dp30 with large variation in sulfation and sequence composition ( 125 , 149 , 150 ). As one of the most sensitive analytical techniques, MS is well suited for this type of analysis, particularly when HPLC or CZE is used to separate the mixtures ( 131 , 144 ).…”

Section: Applicationsmentioning

confidence: 99%

“…Several groups have analyzed GAG oligomers up to dp30 using HILIC-LC-MS(65,125,126). Using a maltose modified HILIC column and high resolution MS, Sun et al separated and identified 36 building blocks that comprise the nitrous acid depolymerized LMWH mixtures, dalteparin and nadroparin(127). Over 30 building blocks were separated within one hour without derivatization of the oligosaccharides.…”

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confidence: 99%

Developments in Mass Spectrometry for Glycosaminoglycan Analysis: A Review

Pepi

Sanderson

Stickney

et al. 2021

Molecular & Cellular Proteomics

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This review covers recent developments in glycosaminoglycan (GAG) analysis via mass spectrometry (MS). GAGs participate in a variety of biological functions, including cellular communication, wound healing, and anticoagulation, and are important targets for structural characterization. GAGs exhibit a diverse range of structural features due to the variety of O- and N-sulfation modifications and uronic acid C-5 epimerization that can occur, making their analysis a challenging target. Mass spectrometry approaches to the structure assignment of GAGs have been widely investigated, and new methodologies remain the subject of development. Advances in sample preparation, tandem MS techniques (MS/MS), on-line separations and automated analysis software have advanced the field of GAG analysis. These recent developments have led to remarkable improvements in the precision and time efficiency for the structural characterization of GAGs.

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“…24,27 HILIC has also been coupled with triple quadrupole M/M with an MRM approach to analyze and quantify heparin building blocks. 49,50 HILIC can be combined with weak anion exchange (WAX) method. Turiák and coworkers 51 coupled self-packed HILIC-WAX capillary columns to a UPLC Q-Tof MS system, revealing that HS disaccharide composition varies in different grades of prostate cancer tissues.…”

Section: Gag Chain Analysismentioning

confidence: 99%

Analysis of the Glycosaminoglycan Chains of Proteoglycans

Song

Zhang

Linhardt

2020

J Histochem Cytochem.

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Glycosaminoglycans (GAGs) are heterogeneous, negatively charged, macromolecules that are found in animal tissues. Based on the form of component sugar, GAGs have been categorized into four different families: heparin/heparan sulfate, chondroitin/dermatan sulfate, keratan sulfate, and hyaluronan. GAGs engage in biological pathway regulation through their interaction with protein ligands. Detailed structural information on GAG chains is required to further understanding of GAG–ligand interactions. However, polysaccharide sequencing has lagged behind protein and DNA sequencing due to the non-template-driven biosynthesis of glycans. In this review, we summarize recent progress in the analysis of GAG chains, specifically focusing on techniques related to mass spectroscopy (MS), including separation techniques coupled to MS, tandem MS, and bioinformatics software for MS spectrum interpretation. Progress in the use of other structural analysis tools, such as nuclear magnetic resonance (NMR) and hyphenated techniques, is included to provide a comprehensive perspective.

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Hydrophilic interaction chromatography-multiple reaction monitoring mass spectrometry method for basic building block analysis of low molecular weight heparins prepared through nitrous acid depolymerization

Cited by 29 publications

References 22 publications

Heparanase as an Additional Tool for Detecting Structural Peculiarities of Heparin Oligosaccharides

Heparanase as an Additional Tool for Detecting Structural Peculiarities of Heparin Oligosaccharides

Developments in Mass Spectrometry for Glycosaminoglycan Analysis: A Review

Analysis of the Glycosaminoglycan Chains of Proteoglycans

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