The rapid identification of drug metabolites using capillary liquid chromatography coupled to an ion trap mass spectrometer

Capillary liquid chromatography (LC) using a 320 mu m column and a flow rat e of 10 mu L/min has been coupled to an ion trap mass spectrometer using el ectrospray ionisation (ESI) to enable the rapid and effective identificatio n of metabolites in urine, following oral administration of a novel human n eutrophil elastase inhibitor, GW311616, Metabolites were identified from th eir mass (MS) spectra and tandem (MS/MS) mass spectra using minimal sample (1 mu L of urine) and no sample pretreatment, Sensitivity assessment has sh own that both molecular weight and structural information is obtainable on as little as 5 pg of compound, making the capillary LC/ion trap system as d escribed an ideal analytical tool for the detection and characterisation of low level metabolites in biofluids (particularly when sample volume is lim ited). This level of detection was unattainable using a triple quadrupole m ass spectrometer operating In full-scan mode, although 200 fg on column was detected using selected reaction monitoring target analysis. Copyright (C) 1999 John Whey & Sons, Ltd.