Improving Standard LC-MS Bioanalysis Approaches of siRNA Therapeutics from Tissues

Oligonucleotide therapeutics have emerged as a novel drug modality, offering superior specificity and the ability to treat rare diseases. As the field advances, there's a growing demand for improved bioanalytical tools to characterize these complex molecules. Recently, we've seen increased interest in the bioanalysis of tissue samples to characterize distribution and accumulation.
Liquid chromatography-mass spectrometry (LC-MS) has gained popularity for oligonucleotide bioanalysis in tissue samples due to its superior selectivity and ability to distinguish closely related metabolites. However, tissue bioanalysis remains challenging due to the complexity associated with various tissue types, which can impact sample preparation, extraction, and LC-MS analysis.
This rapid-fire presentation will summarize our recent experiences with the bioanalysis of oligonucleotides from tissues, including example data from case studies. We will highlight key methodological differences between plasma and tissue matrices. Additionally, we will emphasize critical details in sample preparation, extraction, and LC-MS/MS analysis for various tissue types. These methodological improvements allow for more standardized approaches, enhancing method development efficiency and robustness.