The use of high‐performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC/ICPMS) with sulphur‐specific detection was investigated as a method for obtaining metabolite profiles for the drug omeprazole administered as a 1:1 mixture of ³²S‐ and ³⁴S‐labelled material. Analysis based on the monitoring of the chromatographic eluent at either m/z 32 or 34 was not successful due to insufficient sensitivity caused by interferences from polyatomic ions. However, reaction of sulphur with oxygen in the hexapole collision cell, combined with monitoring at m/z 48 (for ³²S) or m/z 50 (for ³⁴S), provided a facile method for metabolite profiling. Detection of m/z 48 was superior in sensitivity to detection of m/z 50. Copyright © 2003 John Wiley & Sons, Ltd.