Anal. Chem. 1995,67,4091-4095
Optimization of NMR and HPLC Conditions for LC-NMR Lee Griffiths Pharmaceutical Department, ZENECA Pharmaceuticals, Hurdsfield Industrial Estate, Macclesfield, Cheshire SK10 2NA, U.K.
The N M R sensitivity was recognized as the major issue in the optimization of the coupled HPLC-NMR experiment. Each of the relevant interactions between HPLC parameters and NMR parameters has been examined in detail such that workers should be able to design a strategy to optimize their own experiments. The coupling of NMR and HPLC is not a new concept: a physical link has existed for several Indirect links, Le., sequential preparative HPLC and then NMR, have existed even longer and are probably still used more widely than LC-NMR One-off requirements are probably more easily satisfied by sequential preparative LC and NMR, where the time taken to remove protonated solvent and transfer it to an NMR tube is small compared to the time taken to change the NMR probe. Where many NMR problems require preseparation by LC, LCNMR coupling becomes expedient, and the decision whether to do preparative LC and then NMR or coupled LC-NMR (apart from the availability of a probe) depends on the amount of material involved. Typical 4.6” LC column loadings are of the order of 10pg, very much at the lower limit of detection of NMR, especially where a minor component (
