Multiple hyphenation of liquid chromatography with nuclear magnetic resonance spectroscopy, mass spectrometry and beyond

The advent of sensitive and reliable HPLC–NMR and HPLC–MS systems has revolutionised the identification of compounds eluting from chromatographic systems. More recently systems have been described wherein both NMR and MS are used together to provide an immensely powerful means of characterising compounds in chromatographic eluents. Here the construction and application of combined HPLC–NMR–MS systems to the analysis of mixtures of pharmaceuticals, drug metabolites in biological fluids and natural products in plant extracts is reviewed. In addition preliminary work with alternative systems such as HPLC–UV–NMR–FTIR–MS is highlighted and the prospects for such complex systems considered.