Linking HPLC with NMR

Linking techniques together might seem like a good idea in theory but in practise, there can be as many problems as potential advantages. HPLC-NMR does have undeniable use in the field of bio-fluid NMR and in process control in a production environment but we feel that it has little to offer the organic chemist looking to monitor a reaction. 

Essential Practical NMR for Organic Chemistry S. A. Richards and J. C. Hollerton 

There are numerous other problems associated with the technique. Such systems need very careful setting up to ensure that the fractions park accurately in the flow cell so as to maximise concentration and hence signal to noise. Other minor irritants can include various plumbing problems, blockages causing capillaries to burst off, wet carpets etc. 

There are several variations on the theme of instrument set up, which have been used in an attempt to overcome the shortcomings inherent in the concept. For example, as an alternative to the stop-flow method, the various fractions can be collected into sample loops (small loops of capillary tubing) which can then be flushed into the flow cell and studied at leisure. After spectroscopic examination, each sample can then be returned to its loop and the next pumped in. Fractions suffer dilution in this way but this approach would seem to offer an advantage over stop-flow in that at least the chromatography is not compromised by diffusion on the column. 

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