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"Optimizing Sample Preparation for Accurate LC‑MS Analysis of Oligonucleotides"

Empower more accurate, reliable oligonucleotide analysis with optimized sample preparation strategies that reduce matrix complexity, improve LC‑MS sensitivity, and accelerate discovery.

• Oligonucleotide‑based therapeutics are rapidly reshaping drug discovery, but their structural complexity and diverse impurity profiles present significant analytical challenges.
• This white paper examines why optimized sample preparation—particularly solid‑phase extraction (SPE)—is essential for achieving reliable, high‑sensitivity LC‑MS analysis.
• Through a series of controlled experiments using weak anion exchange SPE, the paper demonstrates how variables such as wash conditions, elution strength, volume, and number of aliquots directly influence recovery, matrix cleanliness, and analytical consistency.
• The findings highlight a systematic approach for optimizing SPE protocols to reduce matrix interference, prevent phospholipid buildup, and ensure accurate characterization of oligonucleotides throughout development.

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