Hyphenated HPLC-NMR and its applications in drug discovery

Hyphenated HPLC-NMR is a fast growing technology, allowing rapid and detailed structural characterization of unknown mixtures. The technical aspects of the technology are reviewed on the basis of system configuration, operation, solvent suppression, HPLC and NMR optimization, and detection. The combined use of HPLC-NMR and HPLC-MS is also described and discussed. Various applications of HPLC-NMR and integrated HPLC-NMR-MS in drug discovery, especially in the separation and structure elucidation of drug impurities, reaction mixtures, degradation products, in vitro and in vivo metabolites, and combinatorial library samples, are illustrated.