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High-Performance Liquid Chromatography Nuclear Magnetic Resonance

Nuclear Magnetic Resonance and Electron Spin Resonance Spectroscopy

  1. Harry C. Dorn

Published Online: 15 SEP 2006

DOI: 10.1002/9780470027318.a6106

Encyclopedia of Analytical Chemistry

Encyclopedia of Analytical Chemistry

How to Cite

Dorn, H. C. 2006. High-Performance Liquid Chromatography Nuclear Magnetic Resonance. Encyclopedia of Analytical Chemistry. .

Author Information

  1. Virginia Polytechnic Institute and State University, Blacksburg, USA

Publication History

  1. Published Online: 15 SEP 2006


The direct coupling of high-performance liquid chromatography (HPLC) to nuclear magnetic resonance (NMR) has evolved as a powerful new tool (HPLC/NMR) for the analysis of mixtures. The technique was originally reported in the late 1970s, but was generally limited by NMR detector sensitivity constraints and the availability of routine high magnetic field dispersion instruments (11.8–17.6 T, 500–750 MHz 1H-NMR). During the early 1980s, the HPLC/NMR technique was applied to problems involving the analysis of mixtures that were typically not sample limited, such as petroleum fuels. In the early 1990s, the advent of commercial HPLC/NMR equipment provided the impetus for a worldwide growth spurt of the HPLC/NMR technique. As outlined in this review, the HPLC/NMR technique has evolved as a powerful tool for applications involving polymers, pharmaceuticals, and biological mixtures.

An inherent advantage of HPLC/NMR is the ability to monitor the NMR chemical shift dimension. This dimension is particularly relevant for those applications involving structural isomer identification and has distinct advantages in comparison with the more commonly employed HPLC/MS (mass spectrometry) technique. Although sensitivity limitations of NMR as a detector are still a concern, the development of more complex hyphenated combinations (such as HPLC/NMR/MS) will undoubtedly continue, especially in the areas of pharmaceutical and drug development. Other technical and phenomenological considerations of the HPLC/NMR technique are presented in this review. Finally, a number of related variant techniques including capillary electrophoresis nuclear magnetic resonance (CE/NMR), capillary zone electrophoresis (CZE), capillary electrochromatography (CEC), supercritical fluid chromatography (SFC), and dynamic nuclear polarization (DNP) are also discussed.