Polyamine co-matrices for matrix-assisted laser desorption/ionization massspectrometry of oligonucleotides

The analysis of oligonucleotides using matrix-assisted laser desorption/ion ization mass spectrometry (MALDI-MS) has led to the investigation of the us e of matrix additives (i.e., co-matrices) to help improve the poor spectral quality commonly observed during the analysis of this class of compounds. The use of certain matrix additives in MALDI-MS has been investigated previ ously, and these additives have been shown to enhance the desorption/ioniza tion efficiency of oligonucleotides during the MALDI experiment. Specifical ly, amine bases, such as piperidine, imidazole, and triethylamine, have bee n shown to improve mass spectral quality as assessed by improved molecular ion resolution and increased molecular ion abundance. These improvements oc cur due to competition between the oligonucleotide and the co-matrix for pr otons generated during the MALDI event, Co-matrices with proton affinities near or above the proton affinities of the nucleotide residues serve as pro ton sinks during the desorption/ionization process, In this work, we have i nvestigated the use of polyamines as co-matrices for MALDI mass spectrometr ic analysis of oligonucleotides, Spermine tetrahydrochloride, spermine, spe rmidine trihydrochloride, and spermidine were evaluated for their effective ness at enhancing the mass spectral quality of oligonucleotides analyzed us ing MALDI-MS, The solution-phase pK(b) values and the gas-phase proton affi nities of these polyamines were determined, and it was found, that the poly amines appear to be more basic than the monofunctional amines investigated previously, The mass spectral data shows that spermidine and spermine ape e xtremely effective co-matrices, yielding improved molecular ion resolution and molecular ion abundances. The spermine co-matrices are more effective t han the spermidine co-matrices, but adduction problems with the spermine co -matrices limits their overall utility. In general, polyamine co-matrices a re found to be more effective than monofunctional amine co-matrices at impr oving the mass spectral data obtained during MALDI-MS of oligonucleotides, Copyright (C) 1999 John Wiley & Sons, Ltd.