Superheated heavy water can be used as the eluent for reversed-phase chroma
tography with on-line HPLC-NMR and HPLC-NMR-MS detection. The method has be
en demonstrated for the separation of model drugs (analgesics and caffeine)
on a poly(styrene - divinylbenzene) stationary phase in isothermal and tem
perature-programmed modes. One- and two-dimensional spectra could be obtain
ed with less interference from the mobile phase than with conventional HPLC
-NMR eluents. Unlike supercritical fluid chromatography-NMR, the spectra co
uld be measured at room temperature and atmospheric pressure. The combinati
on of superheated water HPLC-NMR-MS chromatography enables both NMR and MS
spectra to be obtained simultaneously for the same sample.