Abstract
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.
Highlights
One of the most important pharmaceutically relevant polymers and as well the gold standard in medicine for a stealth effect by the PEGylation reaction is the well-established methoxy poly(ethylene glycol)s (mPEG), which is approved by the Food and Drug Administration (FDA) for a range of applications [1,2,3,4]
We have demonstrated and explained how PEGdiol impurities in widely used mPEGs can be identified rapidly by fast liquid chromatography on C18-derivatized monolithic silica rods
The selection of this stationary phase was based on its particular properties characterized by an open, 4
Summary
One of the most important pharmaceutically relevant polymers and as well the gold standard in medicine for a stealth effect by the PEGylation reaction is the well-established mPEG, which is approved by the Food and Drug Administration (FDA) for a range of applications [1,2,3,4]. Polymers 2018, 10, x FOR PEER REVIEW cross-linkingproblem of proteins other pharmaceutical components resultingwhich in ill-defined well-known of or outmost significance is the existence of ofinterest, PEGdiolthus impurities, lead to species in PEGylation reactions [3]. Approaches from the literature used to address spectrometry (MS) [8],e.g., andnuclear last butmagnetic not least the potential application of liquid[5,6,7], chromatography [9,10,11,12], this problem include, resonance spectroscopy mass spectrometry often hyphenated with suitable detection technology, e.g., evaporative light scattering detection (MS) [8], and last but not least the potential application of liquid chromatography [9,10,11,12], often (ELSD), MS, with etc. Common analytical approaches in polymer science such as matrix-assisted laser desorption
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