Cargando…

Fast Screening of Diol Impurities in Methoxy Poly(Ethylene Glycol)s (mPEG)s by Liquid Chromatography on Monolithic Silica Rods

The determination of diol impurities in methoxy poly(ethylene glycol)s (mPEG)s is of high importance, e.g., in the area of pharmaceutical applications, since mPEGs are considered the gold standard—based on properties of biocompatibility, stealth effect against the immune system, and well-established...

Descripción completa

Detalles Bibliográficos
Autores principales: Brunzel, Michaela, Majdanski, Tobias C., Vitz, Jürgen, Nischang, Ivo, Schubert, Ulrich S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401720/
https://www.ncbi.nlm.nih.gov/pubmed/30961320
http://dx.doi.org/10.3390/polym10121395
_version_ 1783400211492634624
author Brunzel, Michaela
Majdanski, Tobias C.
Vitz, Jürgen
Nischang, Ivo
Schubert, Ulrich S.
author_facet Brunzel, Michaela
Majdanski, Tobias C.
Vitz, Jürgen
Nischang, Ivo
Schubert, Ulrich S.
author_sort Brunzel, Michaela
collection PubMed
description The determination of diol impurities in methoxy poly(ethylene glycol)s (mPEG)s is of high importance, e.g., in the area of pharmaceutical applications, since mPEGs are considered the gold standard—based on properties of biocompatibility, stealth effect against the immune system, and well-established procedures used in PEGylation reactions. Herein, we communicate a straightforward and fast approach for the resolution of the PEGdiol impurities in mPEG products by liquid chromatography on reversed-phase monolithic silica-rods. Thus, we utilize fine, in-house prepared and narrow dispersity mPEGs (Ð ≤ 1.1) and commercial PEGdiol standards as a reference. Most efficient analysis of diol impurities becomes possible with reversed-phase liquid chromatography that results in selective elution of the PEGdiol from mPEG macromolecule populations in partition/adsorption mode. We do this by a minimum selectivity of the population of macromolecules characterizing the narrow molar mass distributions of mPEG. Control experiments with intentionally added water at the start of the well-controlled mPEG synthesis via the living anionic ring opening polymerization of ethylene oxide clearly reconciled the existence of PEGdiol impurity in chromatographed samples. The here-demonstrated methodology allows for the resolution of diol impurities of less than one percent in elution times of only a few minutes, confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) of the collected elution fractions. The unique combination of the open flow-through pore structure of the monolithic silica rods and resultant varying accessibility of C18-derivatized pore surfaces indicates beneficial properties for robust and end-group-specific adsorption/partition liquid chromatography of synthetic macromolecules.
format Online
Article
Text
id pubmed-6401720
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-64017202019-04-02 Fast Screening of Diol Impurities in Methoxy Poly(Ethylene Glycol)s (mPEG)s by Liquid Chromatography on Monolithic Silica Rods Brunzel, Michaela Majdanski, Tobias C. Vitz, Jürgen Nischang, Ivo Schubert, Ulrich S. Polymers (Basel) Communication The determination of diol impurities in methoxy poly(ethylene glycol)s (mPEG)s is of high importance, e.g., in the area of pharmaceutical applications, since mPEGs are considered the gold standard—based on properties of biocompatibility, stealth effect against the immune system, and well-established procedures used in PEGylation reactions. Herein, we communicate a straightforward and fast approach for the resolution of the PEGdiol impurities in mPEG products by liquid chromatography on reversed-phase monolithic silica-rods. Thus, we utilize fine, in-house prepared and narrow dispersity mPEGs (Ð ≤ 1.1) and commercial PEGdiol standards as a reference. Most efficient analysis of diol impurities becomes possible with reversed-phase liquid chromatography that results in selective elution of the PEGdiol from mPEG macromolecule populations in partition/adsorption mode. We do this by a minimum selectivity of the population of macromolecules characterizing the narrow molar mass distributions of mPEG. Control experiments with intentionally added water at the start of the well-controlled mPEG synthesis via the living anionic ring opening polymerization of ethylene oxide clearly reconciled the existence of PEGdiol impurity in chromatographed samples. The here-demonstrated methodology allows for the resolution of diol impurities of less than one percent in elution times of only a few minutes, confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) of the collected elution fractions. The unique combination of the open flow-through pore structure of the monolithic silica rods and resultant varying accessibility of C18-derivatized pore surfaces indicates beneficial properties for robust and end-group-specific adsorption/partition liquid chromatography of synthetic macromolecules. MDPI 2018-12-16 /pmc/articles/PMC6401720/ /pubmed/30961320 http://dx.doi.org/10.3390/polym10121395 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Brunzel, Michaela
Majdanski, Tobias C.
Vitz, Jürgen
Nischang, Ivo
Schubert, Ulrich S.
Fast Screening of Diol Impurities in Methoxy Poly(Ethylene Glycol)s (mPEG)s by Liquid Chromatography on Monolithic Silica Rods
title Fast Screening of Diol Impurities in Methoxy Poly(Ethylene Glycol)s (mPEG)s by Liquid Chromatography on Monolithic Silica Rods
title_full Fast Screening of Diol Impurities in Methoxy Poly(Ethylene Glycol)s (mPEG)s by Liquid Chromatography on Monolithic Silica Rods
title_fullStr Fast Screening of Diol Impurities in Methoxy Poly(Ethylene Glycol)s (mPEG)s by Liquid Chromatography on Monolithic Silica Rods
title_full_unstemmed Fast Screening of Diol Impurities in Methoxy Poly(Ethylene Glycol)s (mPEG)s by Liquid Chromatography on Monolithic Silica Rods
title_short Fast Screening of Diol Impurities in Methoxy Poly(Ethylene Glycol)s (mPEG)s by Liquid Chromatography on Monolithic Silica Rods
title_sort fast screening of diol impurities in methoxy poly(ethylene glycol)s (mpeg)s by liquid chromatography on monolithic silica rods
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401720/
https://www.ncbi.nlm.nih.gov/pubmed/30961320
http://dx.doi.org/10.3390/polym10121395
work_keys_str_mv AT brunzelmichaela fastscreeningofdiolimpuritiesinmethoxypolyethyleneglycolsmpegsbyliquidchromatographyonmonolithicsilicarods
AT majdanskitobiasc fastscreeningofdiolimpuritiesinmethoxypolyethyleneglycolsmpegsbyliquidchromatographyonmonolithicsilicarods
AT vitzjurgen fastscreeningofdiolimpuritiesinmethoxypolyethyleneglycolsmpegsbyliquidchromatographyonmonolithicsilicarods
AT nischangivo fastscreeningofdiolimpuritiesinmethoxypolyethyleneglycolsmpegsbyliquidchromatographyonmonolithicsilicarods
AT schubertulrichs fastscreeningofdiolimpuritiesinmethoxypolyethyleneglycolsmpegsbyliquidchromatographyonmonolithicsilicarods