LC/NMR applications

Compared to other analytical techniques (LC/UV or LC/MS), LC/NMR can be regarded as relatively insensitive due to intrinsic properties of NMR detection, which is a consequence of the small energy gap between ground and excited nuclear spin states. On the other hand, limits of detection will also depend on the type of magnet used, LC/NMR applications have been reported on magnets of 400 up to... 

Due to the lack of sensitivity, most of the LC/NMR applications requires the accumulation of many transients for achieving a satisfactory detection of the compounds of interest. For the recording of detailed structural information, measurement of 2D correlation experiments is also often mandatory. Consequently, LC/NMR can be operated not only in dynamic but also in static conditions. These main operation modes are described below and require different level of automation ... 

There are many examples in the literature of LC/NMR applications in natural products, food analysis, " metabolites, degradation products, drug impu-rities, and drug discovery. 

Wolfender JL, Ndjoko K and Hostettmann K. 2003. Application of LC-NMR in the structure elucidation of polyphenols. In Santos-Buelga C, Williamson G, editors. Methods in Polyphenol Analysis. Cambridge, UK Royal Society of Chemistry, pp. 128-156. 

Of particular importance with the use of LC-NMR as an experimental technique is that it is suited for only a limited number of applications in reference to structure elucidation. As will be discussed in greater detail, the sensitivity issues that arise between the amount of compound one is able to load onto a particular chromatographic stationary phase, and hence elute into the flow-cell of an LC-NMR probe, limit what type of structural analysis that can be performed. It is this author s current opinion that most complete structure elucidations of unknown molecular entities are not amenable to LC-NMR. In these... 

The high sensitivity of hyphenated techniques such as HPLC-MS has also been exploited in the identification and structural studies of flavonoid glucosides [151] and the application of other hyphenated techniques such as LC-MS-MS and LC-NMR for the analysis of plant constituents has been discussed earlier [152],... 

As liquid chromatography plays a dominant role in chemical separations, advancements in the field of LC-NMR and the availability of commercial LC-NMR instrumentation in several formats has contributed to the widespread acceptance of hyphenated NMR techniques. The different methods for sampling and data acquisition, as well as selected applications will be discussed in this section. LC-NMR has found a wide range of applications including structure elucidation of natural products, studies of drug metabolism, transformation of environmental contaminants, structure determination of pharmaceutical impurities, and analysis of biofiuids such as urine and blood plasma. Readers interested in an in-depth treatment of this topic are referred to the recent book on this subject [25]. 

The hyphenation of CE and NMR combines a powerful separation technique with an information-rich detection method. Although compared with LC-NMR, CE-NMR is still in its infancy it has the potential to impact a variety of applications in pharmaceutical, food chemistry, forensics, environmental, and natural products analysis because of the high information content and low sample requirements of this method [82-84]. In addition to standard capillary electrophoresis separations, two CE variants have become increasingly important in CE-NMR, capillary electrochromatography and capillary isotachophoresis, both of which will be described later in this section. 

Undoubtedly high-resolution NMR spectroscopy is one of the most powerful analytical tools for the structure elucidation of organic molecules. The coupling of HPLC and NMR spectroscopy recently has further extended its utility in pharmaceutical analysis and other fields. This section will summarize the applications of LC-NMR to studies of pharmaceutical interest. 

---