Composition mapping of highly substituted cellulose-ether monomers by liquid chromatography-mass spectrometry and probability-based data deconvolution

Cellulose ethers (CEs) are semi-synthetic polymers produced by derivatization of natural cellulose, yielding highly substituted products such as ethyl hydroxyethyl cellulose (EHEC) or methyl ethyl hy-droxyethyl cellulose (MEHEC). CEs are commonly applied as pharmaceutical excipients and thickening agents in paints and drymix mortars. CE properties, such as high viscosity in solution, solubility, and bio-stability are of high interest to achieve required product qualities, which may be strongly affected by the substitution pattern obtained after derivatization. The average and molar degree of substitution often cannot explain functional differences observed among CE batches, and more in-depth analysis is needed. In this work, a new method was developed for the comprehensive mapping of the substitution degree and composition of beta-glucose monomers of CE samples. To this end, CEs were acid-hydrolyzed and then analyzed by gradient reversed-phase liquid chromatography-mass spectrometry (LC-MS) using an acid-stable LC column and time-of-flight (TOF) mass spectrometer. LC-MS provided monomer resolution based on ethylene oxide, hydroxyl, and terminating methyl/ethyl content, allowing the assignment of detailed compositional distributions. An essential further distinction of constitutional isomer distri-butions was achieved using an in-house developed probability-based deconvolution algorithm. Aided by differential heat maps for visualization and straightforward interpretation of the measured LC-MS data, compositional variation between bio-stable and non-bio-stable CEs could be identified using this new approach. Moreover, it disclosed unexpected methylations in EHEC samples. Overall, the obtained molecular information on relevant CE samples demonstrated the method's potential for the study of CE structure-property relationships.(c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Automated summary

Cellulose ethers (CEs) are semi-synthetic polymers derived from natural cellulose, and they exhibit various properties important for pharmaceutical and industrial applications. A new method using liquid chromatography-mass spectrometry (LC-MS) was developed to comprehensively analyze the substitution degree and composition of CE samples. This method allowed for the identification of compositional variations and unexpected methylations in CE samples, providing valuable molecular information for studying CE structure-property relationships.