Therapeutic antibodies offer great promise for targeted gene modulation and the treatment of diseases. There are challenges, however, in the synthesis and purification of OGNs for testing and therapeutic use. Several new gas chromatography systems offer advantages for the detection of residual solvents and other contaminants arising during synthesis. These systems provide solutions to accelerate OGN development and release testing during OGN production and scale-up to manufacturing.
Oligonucleotide (OGN) synthesis and purification are very active areas of research and development. As opposed to more conventional small molecule therapeutics which target proteins and other biological molecules, OGNs target distinct regions of DNA and RNA in which the target sequence is known. This gives them exquisite selectivity for modulating gene expression, splicing, silencing, and other activities. Antisense (ASO) and small interfering RNA (siRNA) are examples of common OGN platforms.
Challenges of OGN therapeutics include stability, tissue-specific targeting, and delivery, and downstream modifications of purified OGNs are essential to addressing these challenges. Contaminants including incomplete OGN synthesis products (shortmers), extraneous or improper additions (longmers), and other side products must be detected and quantified to adjust the workflow for maximal yield. Residual solvents including acetonitrile, ethyl acetate, toluene, and others arising from the starting materials and/or product mixtures of OGN synthesis reactions, present problems in purification and quality testing.
Although there are currently no ICH or FDA regulatory guidelines that specifically address the quality standards for OGN drugs, ICH Q3C(R6) and ICH Q3D guidelines that cover residual solvents, and elemental impurities, respectively, are applicable to OGN products.
The 8890 Gas Chromatograph (GC) System from Agilent can provide fast and accurate results with flexibility to address specific demands including residual solvents analysis.
The system also benefits from built-in intelligence and autonomous diagnostic features. These include:
The system can be mated upstream with the Agilent 8697 Headspace Sampler.
The Agilent Intuvo 9000 is the ultimate GC system for fast, high-throughput, and simplified workflows. Specifications include:
Smart features include:
Mating with the 7697A Head Space Sampler ensures leak-free operation, with no loss of precision or sensitivity. Hydrogen can safely be used as an alternative carrier gas as well.
Take a closer look at the browser interface of the 8890 and Intuvo 9000 GC systems
The Agilent 5977C GC/MSD is a routine and reliable workhorse for environmental impurities and food testing, chemical and petrochemical analysis, as well as the analysis of forensic and pharmaceutical compounds. The specs and features of this single quadrupole system make it well-suited for oligonucleotide analysis and residual solvent detection.
Advances features include:
Read about the technical details of the new InertPlus system and the benefits of transitioning to H2 carrier gas.
As the territory for potential oligonucleotide therapeutics expands, so does the range of new purification and testing technologies. Identifying and quantitating residual solvents is imperative to building effective OGN development workflows. The systems and configurations described above can deliver high-performance research results while satisfying USP/ICH compliance and release testing requirements for residual solvents.