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 |
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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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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.</description><subject>Biocompatibility</subject><subject>Chain branching</subject><subject>Charge distribution</subject><subject>Chemical synthesis</subject><subject>Conjugation</subject><subject>Deconvolution</subject><subject>Defects</subject><subject>Fourier analysis</subject><subject>Fourier transforms</subject><subject>In vivo methods and tests</subject><subject>Liquid chromatography</subject><subject>Macromolecules</subject><subject>Mass spectra</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Pharmaceuticals</subject><subject>Polydispersity</subject><subject>Polymers</subject><subject>Quality control</subject><subject>Toxicity</subject><issn>0003-2700</issn><issn>1520-6882</issn><issn>1520-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kUFv1DAQhS0EapfSf4CQJS5csoyd2Nkcy0Kh0lat1HKOJs6EurLjYidIy5_gL-N2tz300JM1o-89z9Nj7L2ApQApPqNJSxzRmRvyy8rkVV29YguhJBR6tZKv2QIAykLWAIfsbUq3AEKA0AfssGykbBpVL9i_qykSemdHO_7im3VxfsXXNxjRTBTtX5xsGHkY-GXeeTQ0T9ag45fBbT3FxLstPw1ztBSL64hjGkL0xRdM1POvZML4J7j5wQPHnp-jicEHR2Z2GPOYUqYGMhM_yUm2yaZ37M2ALtHx_j1iP0-_Xa9_FJuL72frk02BUqmpwLoBlI1RGjstdGlErYTqG0F1ziWElgN1soTOQCeHfLdqVkZ0Om_7viYsj9inne9dDL9nSlPrbTLkHI4U5tSWAkDpSmuR0Y_P0NucON_7QK3Kpq6aMlPVjsoRU4o0tHfReozbVkB7X1ibC2sfC2v3hWXZh7353Hnqn0SPDWUAdsC9_OnjFz3_A5FPp3o</recordid><startdate>20240917</startdate><enddate>20240917</enddate><creator>Swansiger, Andrew K.</creator><creator>Crittenden, Christopher M.</creator><creator>Chan, Simon A.</creator><creator>Yang, Samuel H.</creator><creator>Kou, Dawen</creator><creator>Prell, James S.</creator><creator>Chen, Bifan</creator><general>American Chemical Society</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7U5</scope><scope>7U7</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0379-0821</orcidid><orcidid>https://orcid.org/0000-0002-7320-5491</orcidid><orcidid>https://orcid.org/0000-0002-7505-9168</orcidid><orcidid>https://orcid.org/0000-0001-7792-2554</orcidid><orcidid>https://orcid.org/0000-0001-5713-7161</orcidid></search><sort><creationdate>20240917</creationdate><title>Streamlining LC-MS Characterization of Pharmaceutical Polymers by Fourier-Transform-Based Deconvolution and Macromolecular Mass Defect Analysis</title><author>Swansiger, Andrew K. ; 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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.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>39229957</pmid><doi>10.1021/acs.analchem.4c02174</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0003-0379-0821</orcidid><orcidid>https://orcid.org/0000-0002-7320-5491</orcidid><orcidid>https://orcid.org/0000-0002-7505-9168</orcidid><orcidid>https://orcid.org/0000-0001-7792-2554</orcidid><orcidid>https://orcid.org/0000-0001-5713-7161</orcidid></addata></record> |
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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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