Analytical Characterization of Oligonucleotides by Liquid Chromatography- (LC) High Resolution Mass Spectrometry (HRMS) and State-of-the-Art Analytical Software

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Event Overview:

The primary method for characterization and quantitation of synthetic oligonucleotides is liquid chromatography-mass spectrometry (LC-MS). Whether for characterizing process and product-related impurities or bioanalytical pharmacokinetic studies, improving method sensitivity is of critical importance. In this presentation, we discuss how LC-MS sensitivity can be improved with mobile phase optimization and column selection. We also demonstrate how one can minimize adduct formation and improve ionization efficiency, which can improve MS sensitivity for improved characterization and quantitation data. We have developed novel automatic identification of process-related impurities using high resolution MS (HRMS), new LC columns for oligo analysis, and novel deconvolution / mass-matching software. The methods enable precise characterization of diverse oligonucleotides, with every oligo examined to date (15 independent oligos) having been successfully analyzed.

Key Learning Objectives:

• Learn the fundamentals of electrospray ionization of oligonucleotides, and how different method parameters can affect performance
• Understand the impact of mobile phase and column chemistry in LC-MS methods for oligonucleotides
• Determine experimental parameters to ensure high sensitivity, robust LC-MS methods for synthetic oligonucleotides
• Harnessing the power of data analysis software with novel deconvolution and mass matching for confident characterization

Who Should Attend:

• Analytical method developers looking to improve separation and method robustness for oligonucleotides
• Bioanalytical scientists needing to improve method sensitivity
• Anyone new to oligonucleotide characterization by LC-MS

Speakers

Larry Brill, PhD
Senior Scientist Phenomenex - Biologics

Laurence M. Brill, Ph.D. is a Sr. Application Scientist, BioPharma at Phenomenex. He has established and developed LCMS-based protein and oligonucleotide analysis methods under several different conditions. He is leading a growing team in these large molecule analyses and others that are under development.

Previously, he was a Principal and Sr. Scientist for Bioanalytical & Protein LCMS at Intertek, Sr. Scientist and Director of Proteomics at Sanford Burnham Medical Research Institute, a Postdoctoral Associate and Principal Investigator at the Genomics Institute of the Novartis Research Foundation, and a Postdoctoral Fellow at the Scripps Research Institute.

Maria Basanta - Sanchez. PhD
Protein Metrics

Maria Basanta -Sanchez joined Protein Metrics in 2019 as a Manager of Western US Sales. Before Maria joined industry, she was a scientist with 10+ yearsof analytical researchwith an unbounded focus on personalized medicine, biomarker discovery, clinical applications and oligonucleotide research. She received her PhD from The University of Manchester, UK.Prior to Protein Metrics she was a Senior Application Scientist at Waters Corporationin the Biopharma division

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