New Method Developed to Map Cellulose Ether Monomer Composition

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A new RPLC–MS method can map the substitution degree and composition of β-glucose monomers of cellulose ethers (CEs), providing detailed compositional distributions and constitutional isomer distributions, thereby identifying compositional variation between bio-stable and non-bio-stable CEs and unexpected methylations in EHEC samples.

Researchers from the Vrije Universiteit Amsterdam in the Netherlands have developed a new method for mapping the composition and degree of substitution of β-glucose monomers in cellulose ether (CE) samples. CEs are semi-synthetic polymers produced by the derivatization of natural cellulose, and are commonly used as pharmaceutical excipients and thickening agents in paints and drymix mortars.

The research, published in the Journal of Chromatography A, found that the average and molar degree of substitution often cannot explain functional differences observed among CE batches, and more in-depth analysis is needed (1). The new method involves acid-hydrolyzing CEs and analyzing them by gradient reversed-phase liquid chromatography–mass spectrometry (RPLC–MS) using an acid-stable LC column and time-of-flight (TOF) mass spectrometer.

RPLC–MS is a technique used for separating and identifying compounds in a sample. In RPLC, the stationary phase is a nonpolar material, and the mobile phase is a polar solvent. This separation mechanism is based on the differing affinities of the sample components for the stationary and mobile phases. In MS, the separated compounds are ionized and detected based on their mass-to-charge ratio. RPLC-MS is widely used in fields such as pharmaceuticals, proteomics, metabolomics, and environmental analysis, among others.

RPLC–MS provided monomer resolution based on ethylene oxide, hydroxyl, and terminating methyl/ethyl content, allowing for the assignment of detailed compositional distributions. An essential further distinction of constitutional isomer distributions was achieved using an in-house developed probability-based deconvolution algorithm.


The researchers were able to use the new method to identify compositional variation between bio-stable and non-bio-stable CEs and to discover unexpected methylations in ethyl hydroxyethyl cellulose (EHEC) samples. The obtained molecular information on relevant CE samples demonstrated the method's potential for the study of CE structure-property relationships.

Cellulose ethers have emerged as an important material for a growing bio-based economy due to their unique physicochemical properties. Molecular characteristics such as water-solubility, high viscosity in solution, and bio-stability, render these CEs highly useful and nontoxic thickening agents and excipients for multiple purposes. The new method developed by the researchers provides a more in-depth understanding of the composition and degree of substitution of cellulose ether monomers, which can lead to improvements in product quality and performance.

Overall, the research demonstrates the potential for RPLC–MS and probability-based deconvolution algorithms to provide detailed compositional mapping of highly substituted cellulose-ether monomers. The researchers hope that the new method will lead to advancements in the development of cellulose ether-based products and further understanding of their properties.


(1) Bos, T. S.; Desport, J. S.; Buijtenhuijs, A.; Purmova, J.; Karlson, L.; Pirok, B. W. J.; Schoenmakers, P. J.; Somsen, G. W. Composition mapping of highly substituted cellulose-ether monomers by liquid chromatography–mass spectrometry and probability-based data deconvolution. J. Chromatogr. A 2023, 1689, 463758. DOI: