Historical Development of LC-NMR

During the last few years, more progress has been achieved by hyphenating LC-NMR to MS. The LC-NMR-MS or LC-NMR/MS (referred to as LC-MS-NMR in this chapter) has expanded the structure-solving capabilities by obtaining simultaneously MS and NMR data from the same chromatographic peak. There are some compromises that have to be taken into account because of the differences between MS and NMR, such as sensitivity, solvent compatibility, and destructive versus nondestructive technique, discussed below. LC-MS has been used for many years as a preferred analytical technique however, with the development of electrospray ionization techniques, LC-MS has been routinely used for the analysis of complex mixtures in the pharmaceutical industry. LC-MS-NMR is a combination of LC-MS with electrospray and LC-NMR presented below. 

Although several other important nuclides can be detected by NMR, proton ( H) remains the most widely used because of its high sensitivity, high isotopic natural abundance (99.985%), and ubiquitous presence in organic compounds. Of comparable importance is carbon ( C), 1.108% abundance, which, because of substantial improvements in instrument sensitivity, is now utilized as routinely as proton. Fluorine ( F), 100% abundance, is less used since it is present in only about 10% of pharmaceutical compounds. Another consequence of the intrinsic low sensitivity of NMR is that virtually all samples require signal averaging to reach an acceptable signal-to-noise level. Depend- 

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