We have investigated the feasibility of simplifying the electrospray i
onization (ESI) mass spectra for mixture analyses through charge state
reduction, Two methods for charge state reduction of gasphase oligonu
cleotide negative ions were evaluated: (1) the addition of acids to th
e oligonucleotide solution and (2) the formation of diamine adducts fo
llowed by dissociation in the interface region, In the first method, t
he efficiency of charge state reduction depends on the pK(a), the conc
entration, and the nature of the acids. Acetic and formic acids were f
ound to be better reagents than HCl, CF3CO2H, and H3PO4. The second me
thod has the advantage that the stability of oligonucleotides is not a
ffected but requires the optimization of the interface dissociation:co
nditions and the amounts of diamine added to the oligonucleotide solut
ion. Both methods show promise for charge state reduction, and results
are presented for two oligonucleotides: d(pT)(12) and d(AGCT). Substa
ntial reduction in spectral complexity upon charge state reduction was
also observed for a four-component mixture of oligonucleotides.