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Mass Spectrometry of Nucleic Acids

Nucleic Acids Structure and Mapping

  1. Julia Gross,
  2. Franz Hillenkamp

Published Online: 15 SEP 2006

DOI: 10.1002/9780470027318.a1416

Encyclopedia of Analytical Chemistry

Encyclopedia of Analytical Chemistry

How to Cite

Gross, J. and Hillenkamp, F. 2006. Mass Spectrometry of Nucleic Acids. Encyclopedia of Analytical Chemistry. .

Author Information

  1. University of Münster, Germany

Publication History

  1. Published Online: 15 SEP 2006

This is not the most recent version of the article. View current version (29 DEC 2015)


Nucleic acids are prone to fragmentation in the ionization process of mass spectrometry (MS). The cause can be found in the polar nature of this analyte class. Following the introduction of the so-called soft-ionization techniques of electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) at the end of the 1980s, mass spectrometric analysis of nucleic acids has gained broader applicability. In combination with further developments of the associated instrumentation and optimized preparation and purification methods, a dramatic enhancement of the mass range, detection sensitivity, and resolution became possible – in routine analysis oligonucleotides up to a length of 50 nucleotides are accessible. At present the necessary quantity of sample is in the subfemtomole range.

This article describes the fundamentals of mass spectrometric analyses of nucleic acids and common applications, such as the analysis of noncovalent complexes, mixture analysis, different sequencing strategies and clinical diagnostics. The focus is on MALDI/MS (matrix-assisted laser desorption ionization/mass spectrometry).