Overcome Metal-Analyte Interactions in Oligonucleotide Analysis

The analysis of oligonucleotide-based therapeutics by LC-UV and LC-MS/MS demands exceptional sensitivity, accuracy, and reproducibility. However, the inherent physicochemical properties of these analytes—specifically their negatively charged phosphodiester backbones—make reliable quantification at low concentrations a significant challenge.
In conventional systems, these negatively charged groups form strong bonds with metals in stainless-steel components. This interaction leads to analyte adsorption within the flow path, resulting in peak broadening, reduced peak area, and compromised quantitative accuracy. While countermeasures like sample flow path conditioning or sacrificial oligonucleotide injections exist, they add unnecessary complexity to your workflow.
This application note explores how replacing stainless-steel components with biocompatible, corrosion-resistant materials and low-adsorption coatings significantly improves analytical performance for metal-sensitive analytes like large RNA and mRNA.
Download this technical note to learn:
- The underlying physicochemical mechanisms of metal-analyte adsorption in oligonucleotide analysis
- The limitations of conventional stainless-steel systems and standard countermeasures
- How the fully inert flow path of the Thermo Scientific™ Vanquish™ Amplify UHPLC Platform minimizes metal interactions to enhance sensitivity and accuracy for complex analytes like AMPcP and large RNA molecules
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