Ion-Pair Reversed-Phase LC/MS Analysis of GalNAc-siRNA Conjugates under Denaturing and Non-Denaturing Conditions

User Benefits

- The LCMS-2050 single quadrupole mass spectrometer and the LabSolutions Insight Biologics analysis software can be used to confirm the molecular weight of GalNAc-siRNA conjugates. - LabSolutions Insight Biologics enables analysis of multiple oligonucleotide sequences at the same time. Nucleobases, linkers, riboses, and base modifications can be added and removed as required.

Introduction

Among oligonucleotide therapeutics, antisense and siRNA therapeutics are actively studied as new modalities for treating genetic and intractable diseases. Oligonucleotide therapeutics modified with N-acetylgalactosamine (GalNAc) have attracted attention as drug delivery systems (DDS) designed to enhance the uptake of these therapeutics into the liver. GalNAc binds to the asialoglycoprotein receptor (ASGPR), which is highly expressed in the liver, and is subsequently internalized into hepatocytes. By exploiting this mechanism, GalNAc-modified oligonucleotide therapeutics can be efficiently delivered into hepatocytes. In many cases, a tri-antennary GalNAc (Tri-GalNAc) structure containing three GalNAc residues is used as a highly efficient ligand for ASGPR. This application describes an example of ion-pair reversed-phase LC/MS analysis of GalNAc-siRNA conjugates using a single quadrupole mass spectrometer under denaturing and non-denaturing conditions.

April 16, 2026 GMT