In MALDI MS analysis of nucleic acids, desalting is usually critical for success. This is especially true for the analysis of nucleic acids longer than 60 nucleotides. In many cases, various adducts of multiple metal cations such as potassium and sodium can become so prevalent that the analysis can provide little information. The abundance of the adducts may also prevent desorption. Ammonium salts such as diammonium hydrogen citrate have been found to be able to alleviate these problems when they are used as co-matrices, although long nucleic acid analysis is still challenging. In the literature, the formation of complex metal adducts in nucleic acid analysis is usually attributed to the high affinity of the alkaline metal cations toward the phosphate groups of nucleic acids. In the context of the ion pair thermal model, the metal adducts can be conceived to be easy to form because of the strong Coulombic attraction force between the metal cations and the phosphates in the plume. Few of the multiple ion pairs in a nucleic acid molecule have sufficient thermal energy to become separable by the ion extraction potential. Ammonium salt co-matrices can alleviate the problem because with ammonium salt in the solid sample, the chance for the phosphate groups to ion pair with alkaline metal cations is lowered, and most or almost all the phosphate groups could pair with ammonium cations. Once in the gas phase, the ammonium and alkaline metal cations in the ion pairs are not easy to exchange, and the ion pairs with ammonium cation can readily neutralize via proton transfer.