Considerations for online analysis

The speed of analysis provided by LC-NMR can potentially give significant efficiency gains over off-line techniques. However, there are several factors that need to be considered before deciding which approach to take  

The number of impurities requiring identification. The automation routines offered by LC-NMR gives large efficiency gains when there are several impurities present in a sample (or multiple samples). 

The level and structural complexity of the impurities. Complex impurities require higher analyte concentrations to acquire two-dimensional experiments in reasonable time frames. Low-level impurities may not give the desired spectral quality. 

Prior knowledge of the type of problem to be solved. For example, if aromatic substitution is suspected in an impurity then the couphng pattern of aromatic protons in a one-dimensional H spectrum is sufficient to distinguish the possible isomers. 

Equipment available (HPLC, automated PSU, SPE, flow probe, high-field spectrometer) will determine the overall LC-NMR sensitivity and levels of impurities that can be analysed. For low-level impurities the time required for multiple trapping on SPE cartridges may also need to be considered [84]. 

---