Antisense Capture Increases Sensitivity of LC-MS for Bioanalysis of Oligonucleotide Therapies
Oligonucleotide (OGN) therapies can require multiple bioanalytical assay formats to measure the active pharmaceutical ingredient in tissues and fluids. Hybridization ELISA is used to measure the levels in fluids such as cerebrospinal fluid or plasma because the concentrations can be too low to detect with LCMS. The levels in tissues are commonly measured by LC-MS/MS or LC-high resolution MS (LC-HRMS) as they are greater than liquid matrices. In this talk hosted by AAPs, we will discuss the design of antisense capture probes and capture efficacy across various shortmer lengths and OGNs containing covalently attached small molecules.
Regulatory agencies and innovators increasingly want to monitor additional components in oligonucleotide assays including glycoforms, shortmers, payloads, and other non-OGN constructs. The challenges are that hybridization ELISA lacks the specificity to monitor multiple components and LC-MS doesn’t have the sensitivity to measure components in clinically relevant liquid matrices. To overcome this challenge, antisense capture can be used to clean up and concentrate the samples to increase the sensitivity of the mass spectrometer to have quantitation limits comparable to hybridization ELISA. Watch this video to learn more.
About the Presenter
Liam Moran, PhD
Director of Bioanalytical Chemistry
Charles River