Tackling Moisture Sensitivity in Oligonucleotide Synthesis: Novel Application of GC-VUV Detection

Maximize yield and purity in Oligonucleotide synthesis using a novel approach to monitoring moisture that couples Gas Chromatography with VUV detection.

Register Free: https://www.chromatographyonline.com/lcgc_w/moisture

Event Overview:

Oligonucleotide therapeutics offer precise, gene-specific interventions, modulating gene expression with minimal off-target effects. This approach can address challenging targets in genetic, oncologic, and neurodegenerative diseases, where traditional therapies often fail. The combination of managing unmet medical needs, treating rare diseases, and offering high target specificity with minimal side effects is driving rapid interest in R&D to develop new oligonucleotide-based medicines.

Oligonucleotide synthesis, typically performed on solid-phase supports, is complex and requires strict control of reaction parameters to ensure optimal yield and purity. Moisture content in reagents is a critical variable—trace amounts of water can cause hydrolysis of nucleotide phosphoramidites, leading to byproducts and reduced synthesis efficiency. Accurate measurement of trace moisture levels is thus essential in oligonucleotide development and manufacturing. Traditionally, this is carried out using Karl Fischer titration (KF), which has a number of disadvantages, including difficulty in detecting trace moisture levels, side reactions affecting accuracy, and the practical speed and operability challenges of delivering measurements by titration.

This webinar will explore the impact of moisture on synthesis and demonstrate how water measurement using gas chromatography (GC) coupled with LUMA’s multichannel vacuum ultraviolet (VUV) detection offers precise, highly sensitive moisture quantification. We will present case studies showing how LUMA’s VUV detection improves moisture monitoring, allowing chemists to better control reaction conditions, increase yields, and reduce unwanted side reactions. This ultimately ensures the production of high-purity oligonucleotides for therapeutic applications.

Key Learning Objectives:

• Develop an understanding of the impact of moisture on oligonucleotide synthesis
• Understand the practical considerations for accurate moisture determination using gas chromatography
• Understand how the LUMA™ Multi-channel Vacuum Ultraviolet Detector can solve some of these challenges

Who Should Attend:

• Oligonucleotide analytical method development scientists
• Oligonucleotide purification method development scientists
• Oligonucleotide process development scientists
• Oligonucleotide quality control scientists
• Oligonucleotide contract development and manufacturing organization labs
• Oligonucleotide developability and development scientists

Speakers:

Sam Whitmarsh, PhD
Director of Analytical Science and Digital Transformation
Catsci Ltd, United Kingdom

Sam Whitmarsh, PhD, has 20 years of R&D experience at AstraZeneca, BP, and CatSci. After completing his PhD at the University of Bristol, he held roles in analytical science at AstraZeneca, founded BP’s United Kingdom mass spectrometry facility, and led the BP Global Analytical Science Network. Whitmarsh joined CatSci as head of scientific operations in 2020 and became director of analytical science and digital transformation in 2022. Whitmarsh is a Royal Society of Chemistry Fellow serving with the Separation Science (SSG) and Chemical Information and Computer Applications (CICAG) interest groups

Giuseppe Giuffrida, PhD
Senior Scientist, Oligonucleotides
CatSci Ltd, United Kingdom

Giuseppe Giuffrida, PhD, is an oligonucleotide scientist with a focus on automated solid-phase synthesis. Since joining CatSci, he has directed his expertise to both the upstream (synthesis, cleavage, and deprotection) and downstream (purification, desalting, and annealing) processes of oligonucleotide manufacturing, utilizing MerMade 12 and 192 synthesizers. During his postdoctoral research at the PORT in Wrocław, Poland, Giuffrida focused on the design and synthesis of sequence-defined oligourethanes with precise monomer order, position, and chirality. Prior to that, while completing his PhD at the University of Bath, he worked on synthesizing and characterizing fluorescent naphthalenediimide-based molecular systems, including an oligopeptide designed to target prostate cancer cells. Giuffrida’s work reflects a passion for the chemistry and automation involved in oligonucleotide synthesis, where he thrives in the hands-on challenges of the process.

Register Free: https://www.chromatographyonline.com/lcgc_w/moisture