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Factors influencing the separation of oligonucleotides using reversed-phase/ion-exchange mixed-mode high performance liquid chromatography columns
Journal article   Peer reviewed

Factors influencing the separation of oligonucleotides using reversed-phase/ion-exchange mixed-mode high performance liquid chromatography columns

Mirlinda Biba, Eileen Jiang, Bing Mao, Daniel Zewge, Joe P Foley and Christopher J Welch
Journal of Chromatography A, v 1304, pp 69-77
23 Aug 2013
PMID: 23859796

Abstract

Strong anion-exchange liquid chromatography Mixed-mode stationary phases siRNA Mixed-mode chromatography Ion-pair reversed-phase liquid chromatography Oligonucleotides
•Mixed-mode stationary phases were evaluated for the analysis of oligonucleotides.•A single column and method can be used for complete oligonucleotide analysis.•Mixed-mode columns with SAX-LC conditions provided the best separation.•SM-C18 column with NaCl salt gradient provided the best peak shape and separation. New mixed-mode columns consisting of reversed-phase and ion-exchange separation modes were evaluated for the analysis of short RNA oligonucleotides (∼20mers). Conventional analysis for these samples typically involves using two complementary methods: strong anion-exchange liquid chromatography (SAX-LC) for separation based on charge, and ion-pair reversed-phase liquid chromatography (IP-RPLC) for separation based on hydrophobicity. Recently introduced mixed-mode high performance liquid chromatography (HPLC) columns combine both reversed-phase and ion-exchange modes, potentially offering a simpler analysis by combining the benefits of both separation modes into a single method. Analysis of a variety of RNA oligonucleotide samples using three different mixed-mode stationary phases showed some distinct benefits for oligonucleotide separation and analysis. When using these mixed-mode columns with typical IP-RPLC mobile phase conditions, such as ammonium acetate or triethylammonium acetate as the primary ion-pair reagent, the separation was mainly based on the IP-RPLC mode. However, when changing the mobile phase conditions to those more typical for SAX-LC, such as salt gradients with NaCl or NaBr, very different separation patterns were observed due to mixed-mode interactions. In addition, the Scherzo SW-C18 and SM-C18 columns with sodium chloride or sodium bromide salt gradients also showed significant improvements in peak shape.

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Industry collaboration
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Web of Science research areas
Biochemical Research Methods
Chemistry, Analytical
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