Standard approaches to LC separation of oligonucleotides include an ion pair, an acid modifier and a C18 column. Attempts have been made to optimize the separation of the full-length product (FLP) and impurities but typically fall short as methods require overloading of highly purified products to observe impurities which can create confounding data. This is further complicated by utilization of nominal mass spectrometry systems that have difficulty in resolving confounding masses. This creates workflows that
require manual processing with subjective results based on the analyst performing the assay. Techniques which utilize a variety of stationary phase chemistries in line with a high-resolution mass spectrometer will be explored for the benefits they provide for streamlined oligonucleotide assays.

Subject area:
Biologics

Objectives (If applicable):
NA

Target Audience (If applicable):
QA Manager
QA Staff
QC Chemist
QC Manager
R&D
Regulatory
Student