Recent Progress in LC - NMR

Analytical methods that connect chromatographs and spectrometers online are called hyphenated techniques,1) and they have attracted attention in recent years as high-throughput analytical methods that provide separation of mixtures at the same time as the spectra of the various components. Since, among these, detailed structural information can be obtained from LCNMR (Fig. 1) that combines high-performance liquid chromatographs (HPLC) and nuclear magnetic resonance spectrometers (NMR), they have been applied widely in the analysis of complex mixtures that contain unknown components, such as impurities and metabolites in pharmaceuticals, natural products and synthetic polymers,3), 4) ever since they were first reported in 1978.2) On the other hand, looking at this from the standpoint of applications in research and development at manufacturers, it cannot be said that they have been sufficiently practical in terms of sensitivity and operability of equipment up to now, and they are not a widespread technique compared with the LC-MS. Since the 2000s, however, there were important favorable changes in the situation, and currently, LC-NMR has become a highly practical analytical method because of increased sensitivity in the NMR devices, such as highly magnetic field magnets and highly sensitive probes, and maturation of peripheral technologies, such as solvent elimination technology and automatic measurement software suitable for multicomponent analysis. Along with describing the fundamental technology for improving the performance of the most recent high-performance LC-NMR (Fig. 2) in this article, we will introduce examples of applications for research and development in fine chemicals: pharmaceuticals and agricultural chemicals. In addition, further combination technologies that link LC-NMR with other detectors have appeared in recent years, and it has become possiRecent Progress in LC-NMR Sumitomo Chemical Co., Ltd. Organic Synthesis Research Laboratory Takashi TOKUNAGA Masahiko OKAMOTO