Determination of oligonucleotide deamination by high resolution mass spectrometry

Claus Rentel; Jaimie DaCosta; Stilianos Roussis; Jonathan Chan; Daniel Capaldi; Bao Mai

doi:10.1016/j.jpba.2019.05.012

Determination of oligonucleotide deamination by high resolution mass spectrometry

J Pharm Biomed Anal. 2019 Sep 5:173:56-61. doi: 10.1016/j.jpba.2019.05.012. Epub 2019 May 6.

Authors

Claus Rentel¹, Jaimie DaCosta¹, Stilianos Roussis¹, Jonathan Chan¹, Daniel Capaldi¹, Bao Mai²

Affiliations

¹ Ionis Pharmaceuticals, Carlsbad, CA 92010, United States.
² Ionis Pharmaceuticals, Carlsbad, CA 92010, United States. Electronic address: bmai@ionisph.com.

PMID: 31121454
DOI: 10.1016/j.jpba.2019.05.012

Abstract

A 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.

Keywords: Antisense oligonucleotides; Deamination; High resolution mass spectrometry; Isotopic distribution.

Publication types

Validation Study

MeSH terms

Deamination
Drug Storage
Mass Spectrometry / methods*
Phosphorothioate Oligonucleotides / analysis*
Phosphorothioate Oligonucleotides / metabolism
Temperature

Substances

Phosphorothioate Oligonucleotides