Highly polar and polyanionic, oligonucleotides occupy a difficult space between small molecules and biologics. Analytical chemists transitioning into this space quickly discover that standard reversed-phase LC-MS protocols lead to matrix interference, disappearing samples, and ion suppression during sub-nanogram analysis.
This executive summary of a recent SCIEX webinar provides a roadmap for overcoming these physical and chemical hurdles. Reclaiming baseline stability and assay sensitivity demands a fundamental shift in how labs approach both front-end sample preparation and overall system hygiene.
Download this executive summary to learn:
- How to mitigate matrix interference in plasma and low-protein tissue homogenates using targeted 1.5-plex extraction workflows
- Which surface passivation protocols and dedicated instrumentation rules are strictly required to prevent sample loss and baseline contamination
- How to balance the precise trade-offs between LC-MS specificity and ligand-binding sensitivity for high-potency therapies
Meet the Expert:
 | Rathna Veeramachaneni, PhD Director, Biopharma LC-MS/MS, KCAS Bio (KS, USA) Rathna Veeramachaneni leads Biopharma LC-MS/MS at KCAS Bio, developing quantitative methods for oligonucleotides, antibody-drug conjugates, and protein therapeutics. Her expertise spans hybrid LC-MS approaches at both protein and peptide levels. She earned her PhD from Duquesne University, where she applied crosslinking mass spectrometry to study membrane ion channel conformations. |
