Desalting of oligonucleotides through precipitation for mass spectrometric analysis

Contamination of sodium ions in oligonucleotides often causes issues in mass spectrometric analysis. This study investigated the efficiency of the combination of ammonium acetate and alcohol in desalting oligonucleotides. It was found that oligonucleotide samples containing up to 4 M NaCl can be effectively desalted through precipitation with ethanol or isopropanol in the presence of 1 or 5 M ammonium acetate. The level of sodium ions was reduced by 2-3 orders of magnitude as determined by atomic emission spectroscopy. The desalted samples were successfully analyzed by direct-infusion electrospray ionization mass spectrometry.