Major problems encountered in HPLC-NMR applications:

Sensitivity limitations that can be partially overcomed by

Using higher magnetic fields

Taking advantages of the improvements in probe technologies. Use of superconducting probes.

Use of microprobes that allows to work with mass-limited samples and very smaller volumes.

Suppression of multiple solvent resonances

Proton chemical shifts of the solvent resonances vary significantly as the composition of the mobile phase changes.

Use of presaturation, shaped-pulses or WET schemes (see Multiple solvent suppression schemes)

Peak broadening on and after column 03MRC448) .