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Nucleic acids are increasingly being considered for therapeutic uses, either to interfere with the function of specific nucleic acids or to bind specific proteins.Their straightforwardness in mechanism and relatively small toxicity over conventional drugs attract many scientists in the field.One of the complexities in developing an LC method for nucleic acids is their large molecular weight (>3000).LC-MS, an important technique used in an early stage of pharmaceutical research, often shows a chromatogram of low separation efficiency.