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

Autor: Swansiger AK; Department of Chemistry and Biochemistry, 1253 University of Oregon, Eugene, Oregon 97403-1253, United States., Crittenden CM; Synthetic Molecule Analytical Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Chan SA; Synthetic Molecule Analytical Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Yang SH; Synthetic Molecule Analytical Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Kou D; Synthetic Molecule Analytical Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Prell JS; Department of Chemistry and Biochemistry, 1253 University of Oregon, Eugene, Oregon 97403-1253, United States.; Materials Science Institute, 1252 University of Oregon, Eugene, Oregon 97403-1252, United States., Chen B; Synthetic Molecule Analytical Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Jazyk: angličtina
Zdroj: Analytical chemistry [Anal Chem] 2024 Sep 17; Vol. 96 (37), pp. 14715-14719. Date of Electronic Publication: 2024 Sep 04.
DOI: 10.1021/acs.analchem.4c02174
Abstrakt: 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.
Databáze: MEDLINE