Chromatographic approaches for the characterization and quality control of therapeutic oligonucleotide impurities
Morsy EL Zahar, Noha; Magdy, N.; El-Kosasy, A. M.; Bartlett, Michael G.;
Abstract
Phosphorothioate (PS) oligonucleotides are a rapidly rising class of drugs with significant therapeutic applications. However, owing to their complex structure and multistep synthesis and purification processes, generation of low-level impurities and degradation products are common. Therefore, they require significant investment in quality control and impurity identification. This requires the development of advanced methods for analysis, characterization and quantitation. In addition, the presence of the PS linkage leads to the formation of chiral centers which can affect their biological properties and therapeutic efficiency. In this review, the different types of oligonucleotide impurities and degradation products, with an emphasis on their origin, mechanism of formation and methods to reduce, prevent or even eliminate their production, will be extensively discussed. This review will focus mainly on the application of chromatographic techniques to determine these impurities but will also discuss other approaches such as mass spectrometry, capillary electrophoresis and nuclear magnetic resonance spectroscopy. Finally, the chirality and formation of diastereomer mixtures of PS oligonucleotides will be covered as well as approaches used for their characterization and the application for the development of stereochemically-controlled PS oligonucleotides.
Other data
Title | Chromatographic approaches for the characterization and quality control of therapeutic oligonucleotide impurities | Authors | Morsy EL Zahar, Noha ; Magdy, N.; El-Kosasy, A. M.; Bartlett, Michael G. | Keywords | diastereomers;impurities;ion-exchange;ion-pair;LC–MS;oligonucleotides | Issue Date | 1-Jan-2018 | Journal | Biomedical Chromatography | Volume | 32 | Issue | 1 | ISSN | 02693879 | DOI | 10.1002/bmc.4088 | PubMed ID | 28869310 | Scopus ID | 2-s2.0-85038107705 |
Attached Files
File | Description | Size | Format | Existing users please Login |
---|---|---|---|---|
2017-Oligo Review pdf.pdf | 754.12 kB | Adobe PDF | Request a copy |
Similar Items from Core Recommender Database
Items in Ain Shams Scholar are protected by copyright, with all rights reserved, unless otherwise indicated.