THE USE OF A CO-MATRIX FOR IMPROVED ANALYSIS OF OLIGONUCLEOTIDES BY MATRIX-ASSISTED LASER DESORPTION IONIZATION TIME-OF-FLIGHT MASS-SPECTROMETRY/

Cation adduction to oligonucleotides and nucleic acids during mass spe ctrometric analysis is a recurrent problem. We have found that the use of organic base solutions of high gas-phase proton affinity, as used previously in electrospray ionization mass spectrometry, can significa ntly reduce the cation adduction problem during matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. A comparison of the u tility of adding imidazole or triethylamine as a co-matrix versus the standard addition of cation exchange resin beads was made. The co matr ices studied were found to be more effective than the cation exchange resin beads at reducing cation adducts from samples containing a high level of salt. The use of co-matrices also appears to improve the gas- phase stability of larger oligonucleotides. MALDI-time-of-flight analy sis of a binary mixture of oligoribonucleotide 27-mers with a co-matri x exhibited less metastable decomposition than the same analysis using cation exchange resin beads. The use of co-matrices may be a viable s trategy for the mass spectrometric characterization of larger oligonuc leotides obtained from media containing a high salt content such as po lymerase chain reaction products. (C) 1997 by John Wiley & Sons, Ltd.