Accurate mass determination of a metabolite of a potential diagnostic imaging drug candidate by high performance liquid chromatography with time-of-flight mass spectrometry

A potential drug candidate containing a multiplicity of sulphur atoms, and one unknown in vivo main metabolite, were analysed with an high performance liquid chromatograph time-of-flight mass spectrometer (LC/TOF-MS). Sensitivity and resolution were compared with those obtained with a quadrupole instrument. The LC/TOF-MS provided a more than 200-fold advantage in sensitivity, higher resolving power for the isotopic envelopes of the molecular ions produced by electrospray, and simple procedures for the determination of elemental composition. The exact masses of the candidate and its main metabolite were determined to within 1.5 to 3 ppm, using a single lock mass correction.