Rentel, Claus, Gaus, Hans, Bradley, Kym, Luu, Nhuy, Kolkey, Kimmy, Mai, Bao, Madsen, Mark, Pearse, Megan, Bock, Brandon and Capaldi, Daniel Assay, Purity, and Impurity Profile of Phosphorothioate Oligonucleotide Therapeutics by Ion Pair-HPLC-MS. J.O.C.

Abstract

The relatively large molecular size, diastereoisomeric nature, and complex impurity profiles of therapeutic phosphorothioate oligonucleotides creates significant analytical challenges for the quality control laboratory. To overcome the lack of selectivity inherent to traditional chromatographic approaches, an ion-pair LCMS method combining UV and MS quantification was developed and validated for more than 35 different oligonucleotide drug substances and products, including several commercialized drugs. The selection of chromatographic and spectrometric conditions, data acquisition and processing, critical aspects of sample and buffer preparation and instrument maintenance, and results from method validation experiments are discussed.

Item Type:	Article
Keywords:	oligonucleotide, LCMS, ion pair, quality control, validation
Date Deposited:	19 Jan 2022 00:45
Last Modified:	19 Jan 2022 00:45
URI:	https://oak.novartis.com/id/eprint/45179