The Next Frontier: Advances in Bioanalytical Methods for Biologics and Oligonucleotides
The rise of biologics, peptides, and oligonucleotides has reshaped pharmaceutical development — and with it, the demands placed on analytical science. These molecules bring enormous therapeutic promise, but their structural complexity challenges traditional analytical workflows. In 2025, new technologies are closing the gap, enabling richer characterization and more reliable quality control than ever before.
Biologics present intricate challenges: post-translational modifications, glycosylation variants, charge heterogeneity, and higher-order structural shifts all impact efficacy and safety. Oligonucleotides add their own hurdles, from sequence confirmation to impurity profiling and stability assessment. Conventional chromatography and mass spectrometry aren’t enough on their own.
The most significant progress has come from advanced mass spectrometry (MS) platforms — high-resolution Orbitrap and Q-TOF systems that enable top-down and bottom-up characterization. Ion mobility is increasingly used to resolve subtle structural differences, while multidimensional chromatography (like 2D-LC) has become essential for separating highly complex mixtures. For oligonucleotides, improved ion-pairing LC approaches and high-accuracy MS now allow full-length sequence confirmation with confidence.
These innovations align with regulatory expectations: agencies now want deep molecular understanding supported by orthogonal methods and robust validation. The shift is clear — characterization is no longer a checkbox exercise but a core part of demonstrating product quality.
For pharmaceutical developers, the result is both opportunity and pressure. Many companies lack the internal expertise to operate the latest MS and 2D-LC platforms or interpret the rich datasets they produce. This is where specialized analytical consultants add immediate value, helping teams select the right technologies, develop and validate compliant methods, and interpret complex results.
As the industry continues its shift toward complex modalities, advanced bioanalytics is becoming not just beneficial — but indispensable.