THERAPEUTIC OLIGONUCLEOTIDES, IMPURITIES, DEGRADANTS, AND THEIR CHARACTERIZATION BY MASS SPECTROMETRY

Oligonucleotides are an emerging class of drugs that are manufactured by solid‐phase synthesis. As a chemical class, they have unique product‐related impurities and degradants, characterization of which is an essential step in drug development. The synthesis cycle, impurities produced during the synthesis and degradation products are presented and discussed. The use of liquid chromatography combined with mass spectrometry for characterization and quantification of product‐related impurities and degradants is reviewed. In addition, sequence determination of oligonucleotides by gas‐phase fragmentation and indirect mass spectrometric methods is discussed. © 2019 John Wiley & Sons Ltd. Mass Spec Rev