Development of hydrophilic interaction chromatography with quadruple time‐of‐flight mass spectrometry for heparin and low molecular weight heparin disaccharide analysis

Ouyang, Yilan; Wu, Chengling; Sun, Xue; Liu, Jianfen; Linhardt, Robert J.; Zhang, Zhenqing

doi:10.1002/rcm.7437

Cited by 21 publications

(7 citation statements)

References 30 publications

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“…RPIP‐HPLC offers fast and effective separations of GAG oligosaccharides that can be coupled to MS for structural analysis. Recently, HILIC has also demonstrated analogous advantages for the separation of GAG oligosaccharides . However, both these HPLC approaches are not considered to provide sufficient retention of intact GAGs.…”

Section: Discussionmentioning

confidence: 99%

Ion chromatography for the separation of heparin and structurally related glycoaminoglycans: A review

Fasciano

Danielson

2016

J of Separation Science

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The global crisis resulting from adulterated heparin in late 2007 and early 2008 revived the importance of analytical techniques for the purity analysis of heparin products. The utilization of ion chromatography techniques for the separation, detection, and structural determination of heparin and structurally related glycoaminoglycans, including their corresponding oligosaccharides, has become increasingly important. This review summarizes the primary HPLC approaches, particularly strong anion exchange, weak ion exchange, and reversed-phase ion-pair, used for heparin purity analysis as well as structural characterization. Strong anion exchange HPLC has been studied most extensively and currently offers the best separation of crude heparin and heparin-like compounds. Weak anion exchange HPLC has been shown to provide shorter analysis times with lower salt concentrations in the mobile phase but is not as widely developed for the separation of all glycoaminoglycans of interest. Reversed-phase ion-pair HPLC offers fast and effective separations of oligosaccharides derived from glycoaminoglycans that can be coupled to mass spectrometry for structural analysis. However, this method generally does not provide sufficient retention of intact glycoaminoglycans.

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Section: Discussionmentioning

confidence: 99%

Ion chromatography for the separation of heparin and structurally related glycoaminoglycans: A review

Fasciano

Danielson

2016

J of Separation Science

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“…The use of organic solvents, low backpressure and superior evaporation makes HILIC highly suitable for LC‐MS. Rare disaccharide compositions of Hep, enoxaparin, and nadroparin have been successfully investigated using HILIC–quadrupole time‐of‐flight MS (Ouyang et al, 2016). Additionally, a HILIC‐MS/MS fragmentation technique for analysis of LMWHs prepared by nitrous acid depolymerization was developed (Sun et al, 2017).…”

Section: Methods and Applications Of Glycosaminoglycan Analysismentioning

confidence: 99%

“…Additionally, HILIC‐MS is highly sensitive and routinely used for the analysis of GAG disaccharides (Antia et al, 2018; Gill et al, 2013; Tóth et al, 2020) and GAG oligosaccharides (Li, Zhang, et al, 2012; Liu et al, 2019; Wu et al, 2019). As a final point, the use of stationary phases with sub‐2 micron particles has further increased the resolution and speed of GAG analysis (Ouyang et al, 2016).…”

Section: Liquid Chromatographic Separation Of Glycosaminoglycansmentioning

confidence: 99%

State‐of‐the‐art glycosaminoglycan characterization

Zappe

Miller

Struwe

et al. 2021

Mass Spectrometry Reviews

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Glycosaminoglycans (GAGs) are heterogeneous acidic polysaccharides involved in a range of biological functions. They have a significant influence on the regulation of cellular processes and the development of various diseases and infections. To fully understand the functional roles that GAGs play in mammalian systems, including disease processes, it is essential to understand their structural features. Despite having a linear structure and a repetitive disaccharide backbone, their structural analysis is challenging and requires elaborate preparative and analytical techniques. In particular, the extent to which GAGs are sulfated, as well as variation in sulfate position across the entire oligosaccharide or on individual monosaccharides, represents a major obstacle. Here, we summarize the current state-of-the-art methodologies used for GAG sample preparation and analysis, discussing in detail liquid chromatograpy and mass spectrometry-based approaches, including advanced ion activation methods, ion mobility separations and infrared action spectroscopy of mass-selected species.

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“…High performance liquid chromatography–mass spectrometry (HPLC-MS) has become a widely used method for the analysis of GAG disaccharide composition as it provides confirmation of disaccharide identity based on both retention time and molecular mass. , A number of LC separation methods compatible with MS analysis have been applied to separate GAG disaccharides. Hydrophilic interaction chromatography (HILIC), which was first developed by Zaia and co-workers, can provide excellent separation of underivatized GAG disaccharides. − Alternatively, reverse-phase (RP) separation of ion-paired or derivatized GAG disaccharides on a C18 column affords excellent separation of mixtures containing up to 17 different GAG disaccharides. , …”

Section: Introductionmentioning

confidence: 99%

Negative-Ion Mode Capillary Isoelectric Focusing Mass Spectrometry for Charge-Based Separation of Acidic Oligosaccharides

Ouyang

Han

Xia³

et al. 2018

Anal. Chem.

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Glycosaminoglycans (GAGs) are biologically and pharmacologically important linear, anionic polysaccharides containing various repeating disaccharides sequences. The analysis of these polysaccharides generally relies on their chemical or enzymatic breakdown to disaccharide units that are separated, by chromatography or electrophoresis, and detected, by UV, fluorescence, or mass spectrometry (MS). Isoelectric focusing (IEF) is an important analytical technique with high resolving power for the separation of analytes exhibiting differences in isoelectric points. One format of IEF, the capillary isoelectric focusing (cIEF), is an attractive approach in that it can be coupled with mass spectrometry (cIEF-MS) to provide online focusing and detection of complex mixtures. In the past three decades, numerous studies have applied cIEF-MS methods to the analysis of protein and peptide mixtures by positive-ion mode mass spectrometry. However, polysaccharide chemists largely rely on negative-ion mode mass spectrometry for the analysis of highly sulfated GAGs. The current study reports a negative-ion mode cIEF-MS method using an electrokinetically pumped sheath liquid nanospray capillary electrophoresis–mass spectrometry (CE-MS) coupling technology. The feasibility of this negative-ion cIEF-MS method and its potential applications are demonstrated using chondroitin sulfate and heparan sulfate oligosaccharides mixtures.

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Development of hydrophilic interaction chromatography with quadruple time‐of‐flight mass spectrometry for heparin and low molecular weight heparin disaccharide analysis

Abstract: Thus, compositional analysis using HILIC/QTOFMS offers a unique insight into different heparin products.

Cited by 21 publications

References 30 publications

Ion chromatography for the separation of heparin and structurally related glycoaminoglycans: A review

Ion chromatography for the separation of heparin and structurally related glycoaminoglycans: A review

State‐of‐the‐art glycosaminoglycan characterization

Negative-Ion Mode Capillary Isoelectric Focusing Mass Spectrometry for Charge-Based Separation of Acidic Oligosaccharides

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