A sponsor developing a 17-mer 2’-MOE antisense oligonucleotide (ASO) needed a qualified bioanalytical method to quantify drug levels not only in cerebrospinal fluid, but in brain and spinal cord tissue homogenate matrices that are notoriously difficult for oligonucleotide LCMS work.
Rather than treating the divergence as an instrument or suppression problem by default, Aliri scientists systematically ruled out the
more common explanations and evaluated two extraction chemistries in parallel:
- Liquid-liquid extraction (LLE)
- Phenyl SPE with TEAA/DIPEA chemistry
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