Bioanalysis of Therapeutic Oligonucleotides by HRMS

Gene therapy is among the fastest growing therapeutic modalities and consequently reliable and precise analytical methods are needed to monitor gene therapy toxicology studies and clinical trials. One such solution, high resolution mass spectrometry (HRMS), can deliver accurate and sensitive determination of oligonucleotide drugs in complex matrices.

A pharmacokinetics assessment strategy for siRNA modalities will be presented, featuring ion-pairing reverse phase chromatography and quantitation by QTOF HRMS. Upgrading to the newest SCIEX TripleTOF 6600 System, increased assay sensitivity to 100 pg/mL in plasma.

This standard UPLC HRMS workflow is optimized for medium-high throughput (4 minutes injection-to-injection runtime). Additional metabolite identification in selected samples requires a 20-30 minute runtime on a similar chromatographic platform.

As quantitation is obtained in full-scan mode instead of multiple reaction monitoring, the short quantitative run can be reprocessed afterwards to elucidate metabolic degradation in plasma, excreta, and tissues (kidney, liver).

By attending this webinar, you will:

• Gain understanding about the key aspects of (regulated) bioanalysis of oligonucleotides
• Learn how to define critical parameters in developing quantitative and qualitative HRMS bioanalytical methods for oligonucleotide drugs
• Understand the optimization of sample preparation and MS acquisition for achieving maximum sensitivity and assay performance

Presenter: Fabrizia Fusetti, PhD (Scientific Director, Bioanalysis, QPS)