Ion-pair reversed-phase chromatography analysis of oligonucleotides using ultra-short (20 x 2.1 mm) columns. Tutorial

With this work, we present a comprehensive tutorial for the analysis of oligonucleotides (ONs, 5 to 100 mer) using ion-pair reversed-phase liquid chromatography (IP-RPLC) on ultra-short columns (20 × 2.1 mm). We explore the impact of ion-pairing (IP) agents on ON retention and demonstrate that while...

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Main Authors: Szabolcs Fekete, Mateusz Imiołek, Matthew Lauber
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Journal of Chromatography Open
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772391724000744
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author Szabolcs Fekete
Mateusz Imiołek
Matthew Lauber
author_facet Szabolcs Fekete
Mateusz Imiołek
Matthew Lauber
author_sort Szabolcs Fekete
collection DOAJ
description With this work, we present a comprehensive tutorial for the analysis of oligonucleotides (ONs, 5 to 100 mer) using ion-pair reversed-phase liquid chromatography (IP-RPLC) on ultra-short columns (20 × 2.1 mm). We explore the impact of ion-pairing (IP) agents on ON retention and demonstrate that while IP agents significantly influence absolute retention, their effect on selectivity is often minimal. Our findings emphasize the utility of systematic method development, including software-assisted retention modeling, to optimize gradient steepness and temperature such that resolution can be optimized for both sequence and length variants. We recommend the use of low-adsorption column hardware to minimize nonspecific interactions, which is to the benefit of improving method robustness, peak shapes and recovery (especially of shortmer impurities). Our results confirm the utility of so-called ultra-short column formats as is demonstrated by way of the example, quick run time separations and high-throughput ON analyses. The study establishes practical guidelines for developing robust, reproducible, and high-efficiency IP-RPLC methods for ONs which will be of assistance to analysts working on new therapeutics and new sequencing and diagnostic reagents alike.
format Article
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institution Kabale University
issn 2772-3917
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publishDate 2024-11-01
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series Journal of Chromatography Open
spelling doaj-art-7091a7b2a27c48a698281f30664c32bf2024-12-14T06:34:13ZengElsevierJournal of Chromatography Open2772-39172024-11-016100187Ion-pair reversed-phase chromatography analysis of oligonucleotides using ultra-short (20 x 2.1 mm) columns. TutorialSzabolcs Fekete0Mateusz Imiołek1Matthew Lauber2Waters Corporation, 1 Rue Michel Servet, Geneva 1211, Switzerland; Corresponding author.Waters Corporation, 1 Rue Michel Servet, Geneva 1211, SwitzerlandWaters Corporation, 34 Maple Street, Milford MA 01757, USAWith this work, we present a comprehensive tutorial for the analysis of oligonucleotides (ONs, 5 to 100 mer) using ion-pair reversed-phase liquid chromatography (IP-RPLC) on ultra-short columns (20 × 2.1 mm). We explore the impact of ion-pairing (IP) agents on ON retention and demonstrate that while IP agents significantly influence absolute retention, their effect on selectivity is often minimal. Our findings emphasize the utility of systematic method development, including software-assisted retention modeling, to optimize gradient steepness and temperature such that resolution can be optimized for both sequence and length variants. We recommend the use of low-adsorption column hardware to minimize nonspecific interactions, which is to the benefit of improving method robustness, peak shapes and recovery (especially of shortmer impurities). Our results confirm the utility of so-called ultra-short column formats as is demonstrated by way of the example, quick run time separations and high-throughput ON analyses. The study establishes practical guidelines for developing robust, reproducible, and high-efficiency IP-RPLC methods for ONs which will be of assistance to analysts working on new therapeutics and new sequencing and diagnostic reagents alike.http://www.sciencedirect.com/science/article/pii/S2772391724000744Oligonucleotide separationIon-pairingRetention modelingUltra-short columnPlatform method
spellingShingle Szabolcs Fekete
Mateusz Imiołek
Matthew Lauber
Ion-pair reversed-phase chromatography analysis of oligonucleotides using ultra-short (20 x 2.1 mm) columns. Tutorial
Journal of Chromatography Open
Oligonucleotide separation
Ion-pairing
Retention modeling
Ultra-short column
Platform method
title Ion-pair reversed-phase chromatography analysis of oligonucleotides using ultra-short (20 x 2.1 mm) columns. Tutorial
title_full Ion-pair reversed-phase chromatography analysis of oligonucleotides using ultra-short (20 x 2.1 mm) columns. Tutorial
title_fullStr Ion-pair reversed-phase chromatography analysis of oligonucleotides using ultra-short (20 x 2.1 mm) columns. Tutorial
title_full_unstemmed Ion-pair reversed-phase chromatography analysis of oligonucleotides using ultra-short (20 x 2.1 mm) columns. Tutorial
title_short Ion-pair reversed-phase chromatography analysis of oligonucleotides using ultra-short (20 x 2.1 mm) columns. Tutorial
title_sort ion pair reversed phase chromatography analysis of oligonucleotides using ultra short 20 x 2 1 mm columns tutorial
topic Oligonucleotide separation
Ion-pairing
Retention modeling
Ultra-short column
Platform method
url http://www.sciencedirect.com/science/article/pii/S2772391724000744
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AT mateuszimiołek ionpairreversedphasechromatographyanalysisofoligonucleotidesusingultrashort20x21mmcolumnstutorial
AT matthewlauber ionpairreversedphasechromatographyanalysisofoligonucleotidesusingultrashort20x21mmcolumnstutorial