Matrix-assisted laser desorption ionization time-of-flight mass spectrometry as a rapid quality control method in oligonucleotide synthesis.

Oligonucleotide synthesis is a major activity for a large number of laboratories throughout the world. Dimethoxytrityl-deprotection monitors on instruments give the operator a measure of synthetic efficiency, but cannot be considered as a reliable indicator of the final quality of the cleaved and deprotected oligonucleotide. We have therefore adapted and developed methods of analyzing oligonucleotides by matrix-assisted laser desorption ionization mass spectrometry to the quality control situation, resulting in the ability to analyze 20 oligonucleotides up to at least 40 bases long in less than an hour. Most oligonucleotides can be analyzed automatically using the automatic scanning feature of a Kratos MALDI III analyzer.