TuO-01


RECENT DEVELOPMENTS IN LC/MS/MS AND CE/MS/MS IN DRUG METABOLISM STUDIES

Jack Henion

Cornell University, and Advanced BioAnalytical Services, Ithaca, NY 14850


Electrospray mass spectrometry has evolved from simple "infusion" experiments where the mass spectra of pure compounds or simple mixtures were obtained. More recently, on-line LC/MS and LC/MS/MS techniques are used for the analysis of very complex sample mixtures. The latter has been facilitated by modifications which involve the use of pneumatic assistance of the electrospray process which is often called ion spray. More recently, the use of a hot gas stream has been implemented to further improve the ease of handling higher HPLC flows. Using these and related modifications, LC/MS techniques have become routine in a wide variety of laboratory situations.

Other techniques have also evolved from electrospray ionization. Capillary electrophoresis (CE) has now been coupled with mass spectrometry (CE/MS) and a variety of applications have been reported in the pharmaceutical and environmental areas. The ability to handle very polar analytes with on-line separation and very sensitive detection promises to be of considerable interest in certain applications.

Finally, electrospray LC/MS techniques have provided a very powerful alternative tool for the trace quantitative determination of drugs and their metabolites in biological samples. It is now common to analyze over one-hundred samples per day on one mass spectrometer with detection limits well below a nanogram per milliliter of biological sample. This is all done now with a minimum of sample preparation so that LC/MS techniques are becoming the 'gold standard' for such purposes.

Examples of these analytical capabilities will be presented.