Oligonucleotides
By combining the characteristics of both small molecules and biologics, oligonucleotides represent a unique and promising class of therapeutics. Their ability to precisely modulate gene expression offers new hope for patients with rare and complex genetic conditions. However, this therapeutic potential comes with considerable analytical challenges, demanding high performing, tailored analytical solutions.
A unique analytical approach
At Quality Assistance, we understand that oligonucleotide molecules are unlike any other. That’s why we’ve built a dedicated analytical platform and developed specific methods such as P=O/P=S ratio determination by ICP-MS and impurity profiling using LC-UV-MS to deliver the tailored analysis they require. Our scientific experts don’t just analyse oligonucleotides, they understand their structure, function and clinical relevance.
We design and validate robust analytical strategies adapted to your molecule's specific structure, formulation and clinical context. By using orthogonal techniques and expert scientific guidance, we ensure that critical quality attributes, such as purity and identity meet rigorous regulatory expectations. This allows you to confidently proceed along the path from development to market.
Related products
Analytical challenges we resolve
Developing oligonucleotide-based therapeutics presents unique analytical challenges. We help you address critical questions to ensure product quality and patient safety, from confirming oligonucleotide’s identity to profiling key impurities and degradation products such as shortmers, longmers, PO impurities and diastereoisomers. We also provide strategies for monitoring counter-ions, aggregations, and as well as assessing potency for specific oligonucleotide categories.
Our full range of analytical services includes:
| Intact oligonucleotide | (U)HPLC (UV, MS) |
|---|---|
| Molecular weight | ESI-MS / MALDI-TOF |
| Nucleotide composition / Sequencing | UPLC (UV, MSE) / MALDI-TOF / MS/MS |
| Assay | UV / (U)HPLC (UV, MS) / SoloVPE |
|---|---|
| Absolute oligonucleotide content determination | UV + ICP-MS |
| Determination of extinction coefficient | UV + UPLC (UV) / ICP-MS |
| Purity profile | IEX /RP-(U)HPLC (UV, MS) / HILIC (UV, MS) / cGE |
|---|---|
| Structure | CD / SEC (UV, RI, MALS) |
| Chain lenght | cGE / IEX / RP-(U)HPLC (UV, MS) / HILIC (UV, MS) / SEC (UV, RI, MALS) |
| Molecular backbone composition (P=S / P=O) | ICP-MS |
| Chemical modifications and degradation patterns | ESI-MS / cGE (UV, LIF, MS) / IEX / RP-(U)HPLC (UV, MS) / SEC-MALS / HILIC (UV, MS) / SDS PAGE |
| Aggregation and particle size distribution patterns | AF4 & SEC-(U)HPLC (UV, RI, MALS) / DLS / Imaging particle analysis |
| Enantiomeric purity | (U)HPLC (UV, MS) |
| Counter-ion content | ICP (OES, MS) |
| Cell-based assays (Cytotoxicity) / Proliferative / Cell death / Cell migration / Cell receptor binding and activation / Reporter gene assays / etc. | Different read outs |
| Microbiology | Bioburden / Sterility (filtration, direct inoculation) |
| Endotoxins | LAL (kinetic, end point) / MAT/ rFC |
| Elemental impurities | ICP-MS |
| Residual solvents | HS-GC (FID, MS), HPLC (UV, MS) |
| Leachables | GC (FID, ECD, MS) / ICP (OES, MS) / (U)HPLC (UV, ELSD, CAD, MS) |
|---|---|
| Container Closure System Integrity | Bubbling / Dye ingress / Microbial ingress |
| Cytotoxicity / Biological reactivity | Cell-based assays / USP <87> |
| Break Loose and Glide Force (BLGF) for prefilled syringes |
Platforms and technologies
To address all the challenges you may face in your oligonucleotide product development, we offer a comprehensive set of cutting-edge instrumentation and capabilities:
- Wide range of MS systems including triple and single quadrupoles, QTOF, and MALDI-TOF for routine analysis and high-resolution characterisation
- Liquid chromatography techniques, including Ion-pair RP-LC/UV-MS, IEX and HILIC, as well as Capillary Electrophoresis for efficient separation and characterisation
- ICP-MS/MS for absolute quantification, precise determination of PO/PS ratio and elemental profiling.
- SEC-MALS, Circular Dichroism, Dynamic Light Scattering, for studying higher-order structure and stability.
Related services
Bioanalytical services
Understanding the safety and efficacy of your therapeutic oligonucleotide requires a clear picture of what happens once it's administered to patient. Bioanalysis is the essential tool that gives us this understanding.
Our experts develop and validate robust methods to accurately quantify your molecule in complex biological matrices such as plasma, urine, and tissues. We leverage:
- Advanced techniques like liquid chromatography coupled to mass spectrometry (LC-MS/MS), as well as ligand binding assays, ensuring exceptional sensitivity and specificity even at very low concentrations.
- The establishment of pharmacokinetic profiles, assessing immunogenicity and biomarkers throughout non-clinical and clinical studies.
Why innovators choose us
In the complex world of oligonucleotide development, you need more than a service provider, you need a strategic partner.
- Tailored analytical strategies: we believe a molecule as complex as your oligonucleotide deserves a customised analytical approach. We provide a dedicated platform for oligonucleotides analysis, covering everything from characterisation to final product release and batch testing. We offer specific support for innovative delivery systems and complex formulations.
- Centralised laboratory for full traceability: all analyses are performed in-house, on a single site in Belgium, eliminating the need for outsourcing to multiple sites. This ensures complete traceability and seamless project coordination from start to finish.
- Unmatched compliance and expertise: our laboratory operates under a single GxP environment (GMP, GLP, GCLP/GCP), ensuring compliance with all applicable EMA, FDA, and ICH regulations.
- R&D investments: we make early investments in oligonucleotide-specific methods, such as ICP-MS and LC/MS and provide expert scientific follow-up throughout your project.
- A strategic partner in excellence: our approach is built on a foundation of scientific and technical excellence, coupled with a proactive, problem-solving mindset to guide your project to success with a dedicated customer support team.
Move forward with analytical clarity
We partner with you to navigate your challenges and drive the success of your oligonucleotide projects. Get in touch with our experts to discover our complete range of analytical solutions.