Oligonucleotides have been rapidly gaining attention, as these therapeutic modalities hold high promise to previously untreatable or rare diseases and as better alternatives for common diseases.
They are produced by chemical synthesis and that often results in various product-related impurities, including deletion sequences (‘shortmers’), addition sequences (‘longmers’), and modifications.
Oligonucleotide sequence accuracy is a critical attribute impacting molecular safety profiles and therefore needs to be analysed with high confidence and so LC-MS techniques have been increasingly utilized for their characterization and quantitation.
Many charge deconvolution software programs cannot handle negative-mode mass spectra
There are a variety of instrument vendors and data file formats
Spectra may be isotope-resolved, or not, or a combination depending on the charge
Oligonucleotides are difficult to desalt, and the adduct peaks present an additional complication to peak mass assignment
With the Oligo Workflow within Byos, analytical scientists can perform high throughput oligonucleotide analysis to verify purity and mass confirmation and quantify impurities.
·Automatic or manual integration of chromatographic time windows
·Deconvolution of charge states to transform m/z spectra to neutral mass spectra
·Automatic mass peak picking and intensity calculations
·Sequence confirmation using MS2 fragmentation data
·Confident identification of sequence impurities and degradation products
