Next Generation Sequencing (NGS) Grade
From synthesis, deprotection and downstream processing, every step is optimized to reduce cross-contamination and mutations to yield oligos with the lowest possible error rates.
Therapeutic Grade
Whether your therapeutic lead is an aptamer, ASO, siRNA, sgRNA or an Antibody– or Peptide–Oligo Conjugate, we provide the highest levels of purity and quality control. In addition to providing in depth purity analysis by ESI MS, UPLC and SEC, we also determine endotoxin and moisture content following USP guidelines <86> and <921> respectively, along with sodium, heavy metal content and bioburden.
HPLC Grade
Our HPLC grade oligos are tailored to the requirements of our customers to provide oligos at the purity they need at a price they can afford. Depending upon the sequence length and modifications, we routinely provide oligos with greater than 95% purity by UPLC.
Salt-Free
Our salt-free oligos are synthesized with our same exacting standards but without the added costs of HPLC or PAGE purification. Regardless of oligo length, we guarantee the major peak by ESI MS will be the target mass.
Post Purification QC Methods
- Molecular Weight by Mass Spectrometry
The most preferred method for diagnostic and therapeutic oligos. It is used to confirm the integrity and the molecular weight of the oligo. In ideal scenarios, oligo sequence information can be inferred from MW determination. To get absolute confirmation of sequence, MS/MS or NGS has been used.
- Purity by Chromatography
Liquid chromatography is commonly used to assess the purity of the full-length product and gauge product quality. Separation can be based on reverse-phase, ion exchange, size exclusion, or hydrophobic interaction. In high-throughput modes, a generic LC method (typically reverse-phase) is often used, prioritizing speed over quality.
- Moisture Content
Oligonucleotides are highly hygroscopic, meaning they readily absorb moisture. No matter how long you dry the product, residual water will always remain. This can be determined following USP <921> guidelines.
- Sodium Content
High sodium content can disrupt ion pairing during ion-pair reversed-phase liquid chromatography (RP-LC) analytical separation, altering retention times and causing peak splitting. Additionally, sodium ions can interfere with downstream quality control processes, particularly in mass spectrometry, by suppressing signals due to their high ionization energy and competing with other analytes for ionization. Therefore, measuring and desalting are essential steps to ensure high-quality control of oligonucleotides.um Content
- Endotoxin
Testing ensures that the toxic component, Lipid A, is at or below levels recommended by the United States Pharmacopeia (USP) and FDA. Read our blog post to learn more about the various tests used to assess safety levels.
- Heavy Metal
Screening for metal contamination is becoming increasingly important for product safety. ICH classifies heavy metals into three classes, 1, 2, and 3. Class 1 metals, including As, Cd, Pb, Hg, should be essentially absent as they are known or strongly suspected human toxicants. Class 2 metals, divided into two subcategories A and B based on their probability of occurring in the drug product, include Co, Ni, V as A and Ag, Au, Ir, Os, Pd, Pt, Rh, Ru, Se, and Tl. Class 3 metals have low toxicities in general including Ba, Cr, Cu, Li, Mo, Sb, and Sn.
- Residual Solvents
Residual solvents are categorized into three classes based on toxicity, with Class 1 being the most toxic. To meet high product safety requirements, testing for residual solvents used during synthesis, purification, or in excipients or drug products is necessary. Customers can choose to test the final product or each individual component.
- Bioburden
This test is crucial for determining the number of microbes present in the product. Microbial extraction methods include mechanical testing, vortexing, and sonication. The extract fluid is then used for culturing different organisms and tested by pour plating or filtration.
