There has been noteworthy progress in the oligonucleotide therapeutics field over the past 30 years, beginning with antisense oligonucleotides (ASOs) and aptamers and followed about 15 years ago by siRNAs. Recent innovations in gene editing field is driving the need for oligonucleotides characterization.

MALDI and ESI Mass Spectrometry have prominent roles to play in the life cycle of oligonucleotide drugs from discovery to QC for determination of the molecular weights of natural and synthetic oligonucleotides and in sequencing of DNA and RNA species. Both techniques also have their specific strengths and drawbacks. MALDI-TOF is relatively easy to operate, offers high sensitivity for oligonucleotides, and is well suited to a high-throughput environment. MALDI‐TOF is also reasonably tolerant to the presence of salts, buffers, and other additives. Alternatively, ESI technology maintains high mass accuracy, resolution, and sensitivity over a range of lengths (20–120 bases), but has a reduced throughput and requires more attention to sample cleanliness.

Bruker offers a complete solution for oligonucleotide screening and QC applications with a broad portfolio of innovative and best-in-class MALDI-TOF and UHR ESI-TOF instruments and an integrated software solution for both techniques.

BioPharma Compass 3.1 enables the routine analysis of biopharmaceuticals offering dedicated LC MS workflows including automated measurements and report generation. Both high resolution ESI-QTOF and MALDI-TOF data can be employed for these analyses. Similarity scores and mass accuracy attributes are the basis for an automatic pass/fail assessment. Reports utilize color coding of results and charts for rapid reviewing. Butterfly plots enable visual dataset comparisons.