Studying the Biotransformation of Phosphorothioate-Containing Oligonucleotide Drugs by LC-MS.

ABSTRACT

Across the pharmaceutical industry, there is increasing interest and need to investigate the biotransformation of oligonucleotide drugs. The method of choice is high-resolution mass spectrometry due to its unmet sensitivity and specificity.Here, we describe a method developed and applied in our laboratory studying the biotransformation of phosphorothioate-containing oligonucleotide drugs. This method is based on capillary flow liquid chromatography with column switching coupled to high-resolution mass spectrometry.