Streamlining LC-MS Characterization of Pharmaceutical Polymers by Fourier-Transform-Based Deconvolution and Macromolecular Mass Defect Analysis

Polymer conjugation has risen in importance over the past three decades as a means of increasing the in vivo half-life of biotherapeutics, with benefits including better stability, greater drug efficacy, and lower toxicity. However, the intrinsic variability of polymer synthesis results in products...

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Veröffentlicht in:Analytical chemistry (Washington) 2024-09, Vol.96 (37), p.14715-14719
Hauptverfasser: Swansiger, Andrew K., Crittenden, Christopher M., Chan, Simon A., Yang, Samuel H., Kou, Dawen, Prell, James S., Chen, Bifan
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container_end_page 14719
container_issue 37
container_start_page 14715
container_title Analytical chemistry (Washington)
container_volume 96
creator Swansiger, Andrew K.
Crittenden, Christopher M.
Chan, Simon A.
Yang, Samuel H.
Kou, Dawen
Prell, James S.
Chen, Bifan
description Polymer conjugation has risen in importance over the past three decades as a means of increasing the in vivo half-life of biotherapeutics, with benefits including better stability, greater drug efficacy, and lower toxicity. However, the intrinsic variability of polymer synthesis results in products with broad distributions in chain length and branching structure, complicating quality control for successful functionalization and downstream conjugation. Frequently, a combination of several analytical techniques is required for comprehensive characterization. While liquid chromatography–mass spectrometry (LC-MS) is a powerful platform that can provide detailed molecular features of polymers, the mass spectra are inherently challenging to interpret due to high mass polydispersity and overlapping charge distributions. Here, by leveraging Fourier transform-based deconvolution and macromolecular mass defect analysis, we demonstrate a new way to streamline pharmaceutical polymer analysis, shedding light on polymer size, composition, branching, and end-group functionalization with the capability for reaction monitoring.
doi_str_mv 10.1021/acs.analchem.4c02174
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source American Chemical Society Journals
subjects Biocompatibility
Chain branching
Charge distribution
Chemical synthesis
Conjugation
Deconvolution
Defects
Fourier analysis
Fourier transforms
In vivo methods and tests
Liquid chromatography
Macromolecules
Mass spectra
Mass spectrometry
Mass spectroscopy
Pharmaceuticals
Polydispersity
Polymers
Quality control
Toxicity
title Streamlining LC-MS Characterization of Pharmaceutical Polymers by Fourier-Transform-Based Deconvolution and Macromolecular Mass Defect Analysis
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