LC–NMR–MS in drug discovery

Nuclear magnetic resonance spectroscopy (NMR) is arguably the most versatile analytical platform for complex mixture analysis. Specifically, interfacing liquid chromatography with parallel NMR and mass spectrometry (LC-NMR-MS) gives comprehensive structural data on metabolites of novel drugs in development. Applications in natural product, combinatorial chemistry and drug metabolism studies are reviewed. Microcoil probes and capillary separation methods have enormous potential. Recent innovations to improve NMR detection limits include CryoFlowProbes and on-line solid-phase extraction (LC-SPE-NMR). These state-of-the-art analytical platforms are widely applicable to identifying novel candidate drugs from diverse complex mixtures within a drug discovery strategy.