Double-stranded oligonucleotides of different lengths and chemical mod
ification have been analyzed by ion spray mass spectrometry. The non-c
ovalent-bonded duplexes can be detected. Therefore, ion spray mass spe
ctrometry is a useful method for investigation of hybridizations of na
tural and chemically modified oligonucleotides. Since the exact mass o
f the double strand can be detected, this method can distinguish betwe
en specific and nonspecific interaction.