Contemporary quantitative bioanalytical LC-MS of oligonucleotide and peptide therapeutics


Covance, Somerset (New Jersey), United States


Peptide and oligonucleotide therapeutic development are very important components of the pharmaceutical and biotechnology industries. These therapeutic entities, from preclinical and beyond, require the same bioanalytical method reliability as is synonymous with the regulated laboratory. With a focus on these two particular classes of therapeutic entities, this article covers the reasoning and framework of popular established LC-MS methodologies as well as describing cutting-edge technologies and novel approaches that are coming into use.

The rise of biologics, or biomolecule-based therapeutic candidates in the pharmaceutical and biotech industries has long been anticipated, and has indeed become a reality. In the context of working as a bioanalytical chemist in the contract research environment, it has been clear to see the wave of popularity of peptidic drug candidates reaching a high plateau around ten years ago (1) and, most recently, oligonucleotides as therapeutics has become a pronouncedly hot topic.

Although there are alternative techniques for the quantitative bioanalysis of both peptides and oligonucleotides, such as LC interfaced with UV or fluorescence detection, or non-chromatographic techniques like those involving immunoassay and qPCR, this article is focused on the most selective, reliable and contemporary, the technique of LCMS. Non-chromatographic methodologies have historically enjoyed exquisite sensitivity, but at the expense of poor linear ranges for quantification and, more significantly, a lack of discriminating power to distinguish metabolites or other interferences from the parent therapeutic response, which ties in with selectivity, the most p ...