Confirmation of molecular weight

Molecular characterization of nucleic acids using mass spectrometry is of current growing interest, because oligonucleotide therapeutics are a promising medicine to cure some diseases by working at upper stream of action mechanism with fewer side effects. Whereas a high-resolution accurate ESI mass spectrometer enables an exact intact mass measurement, routine oligo sequence analysis is a still hurdle, using ESI instruments. The complete internal oligo sequence is rarely obtained using typical ESI-MS/MS technique. On the other hand, in-source decay (ISD) using MALDI-TOFMS was reported as a useful method to conduct sequence analysis, although the instruments often employed do not have sufficient specification for exact mass measurement. Here, we report the characterization of oligonucleotide therapeutics using ESI-QTOF and a dual polarity benchtop linear MALDI-TOFMS.