The rapid identification of drug metabolites using capillary liquid chromatography coupled to an ion trap mass spectrometer.
Capillary liquid chromatography (LC) using a 320 microns column and a flow rate of 10 microL/min has been coupled to an ion trap mass spectrometer using electrospray ionisation (ESI) to enable the rapid and effective identification of metabolites in urine, following oral administration of a novel human neutrophil elastase inhibitor, GW311616. Metabolites were identified from their mass (MS) spectra and tandem (MS/MS) mass spectra using minimal sample (1 microL of urine) and no sample pretreatment. Sensitivity assessment has shown 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 described an ideal analytical tool for the detection and characterisation of low level metabolites in biofluids (particularly when sample volume is limited). This level of detection was unattainable using a triple quadrupole mass spectrometer operating in full-scan mode, although 200 fg on column was detected using selected reaction monitoring target analysis.
Dear
G J
GJ
Bioanalysis and Drug Metabolism Division, Glaxo Wellcome Research and Development, Ware, Herts, UK.
Ayrton
J
J
Plumb
R
R
Fraser
I J
IJ
D000818:Animals; D001711:Biotransformation; D002852:Chromatography, Ion Exchange; D002853:Chromatography, Liquid; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D013058:Mass Spectrometry; D008970:Molecular Weight; D010880:Piperidines / Q000378:metabolism; D051381:Rats
D004791:Enzyme Inhibitors; C119405:GW 311616; D010880:Piperidines; D019272:Leukocyte Elastase