Antisense oligonucleotides (ASOs) and newer conjugate modalities, antibody-oligonucleotide conjugates (AOCs) and antibody-siRNA conjugates (ARCs), are expanding treatment options for neurological disease. But route of administration changes everything about the LC-MS/MS strategy needed to support them: intrathecal (IT) dosing produces high, fast-decaying local CSF concentrations, while intravenous (IV) dosing yields much lower CNS exposure after blood-brain-barrier transcytosis, pushing sensitivity requirements to their limits.
This webinar covers how to build LC-MS/MS methods, ion-pairing reversed-phase and hybridization LC-MS/MS, for primary PK quantification across CSF, plasma, and tissue, including how to independently track intact conjugate, free oligonucleotide payload, and antibody component as distinct PK analytes.
What you’ll learn:
- How IT vs. IV dosing shifts expected Cmax, dynamic range, and LLOQ requirements
- Ion-pairing reversed-phase LC-MS/MS method development for oligonucleotides
- When to use hybridization LC-MS/MS for low-abundance targets
- Quantifying intact AOC/ARC conjugate, free payload, and antibody as distinct PK analytes
- Matrix considerations for CSF, plasma, and tissue with limited sample volume