Systematic optimization of ion‐pairing agents and hexafluoroisopropanol for enhanced electrospray ionization mass spectrometry of oligonucleotides

This comprehensive and systematic optimization finds that the hydrophobicity of the oligonucleotide was a key factor in choosing alkylamine ion-pairing agents to increase ESI abundance. We identified that diisopropylamine and tripropylamine combined with lower concentrations of hexafluoroisopropanol yielded the highest signal intensity for these oligonucleotides.