Electrospray mass spectrometry for the characterization of the purity of natural and modified oligodeoxynucleotides.

Electrospray ionization mass spectrometry is an accurate and sensitive analytical method to characterize the purity of oligodeoxynucleotides being tested for pharmacological studies. We report the preparation procedure ('desalting') of natural and modified oligodeoxynucleotides (ODNs) and their analysis by negative-ion electrospray mass spectrometry. We evaluate the sensitivity and the accuracy of the method for two antisense ODN sequences. Mass analysis of the 25-mer phosphorothioate can be performed to within 0.001% accuracy (standard error of 0.05 Da) for a sample concentration of 12 pmol/microL. In addition, the adduct ion and the failure sequence can be identified to characterize the antisense ODN.