Determination of Oligonucleotide Deamination by High Resolution Mass Spectrometry

Publication date: Available online 6 May 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Claus Rentel, Jaimie DaCosta, Stilianos Roussis, Jonathan Chan, Daniel Capaldi, Bao MaiAbstractA novel analytical approach capable of measuring deaminated degradation products of oligonucleotide therapeutics is described. The method employs high-resolution mass spectrometry to assess the shift in isotopic distribution that accompanies deamination. Isotopic Distribution Factors (IDF), derived directly from the peak heights of the isotopic pattern, are employed to measure deamination levels of as little as 0.5%. Results obtained from application of the method to a phosphorothioate diester oligonucleotide exposed to various temperatures were used to determine deamination rates.
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research