A new type of quadrupole linear ion trap mass spectrometer, Q TRAP TM LC/MS/MS system (Q TRAP TM ), was evaluated for its performance in two studies: firstly, the in vitro metabolism of gemfibrozil in human liver microsomes, and, secondly, the quantification of propranolol in rat plasma.With the built-in information-dependent-acquisition (IDA) software, the instrument utilizes full scan MS in the ion trap mode and/or constant neutral loss scans as survey scans to trigger product ion scan (MS 2 ) and MS 3 experiments to obtain structural information of drug metabolites 'on-thefly'. Using this approach, five metabolites of gemfibrozil were detected in a single injection. This instrument combines some of the unique features of a triple quadrupole mass spectrometer, such as constant neutral loss scan, precursor ion scan and multiple reaction monitoring (MRM), together with the capability of a three-dimensional ion trap. Therefore, it becomes a powerful instrument for metabolite identification. The fast duty cycle in the ion trap mode allows the use of full product ion scan for quantification. For the quantification of propranolol, both MRM mode and full product ion scan in the ion trap mode were employed. Similar sensitivity, reproducibility and linearity values were established using these two approaches. The use of the product ion scan mode for quantification provided a convenient tool in selecting transitions for improving selectivity during the method development stage. Copyright # 2003 John Wiley & Sons, Ltd.Liquid chromatography/tandem mass spectrometry (LC/ MS/MS) has been widely applied in both qualitative and quantitative analyses of drug candidates and their metabolites in biological matrices, in support of drug discovery and development. 1-3 Commonly used tandem mass spectrometers include triple stage quadrupole (tandem-in-space), three-dimensional (3D) ion trap (tandem-in-time), and quadrupole time-of-flight (Q-TOF) mass spectrometers. Threedimensional ion trap mass spectrometers are widely used for conducting consecutive product ion scans (MS n ) in a data-dependent fashion that provides useful information for structural elucidation. Triple quadrupole mass spectrometers, on the other hand, can be used to conduct tandem mass scan experiments in various modes including product ion scan (MS 2 ), precursor ion scan, constant neutral loss scan, and multiple reaction monitoring (MRM). The constant neutral loss and precursor ion scan experiments on a triple quadrupole serve as a convenient tool for detecting unknown metabolites in complex biological matrices, especially for phase II drug metabolites, such as acyl glucuronide (loss of 176 Da) and sulfate (loss of 80 Da) conjugates. Thus far, MRM is the most sensitive and selective detection method for confirming trace levels of circulating metabolites in plasma, 4 for example, as in human ADME studies, as well as in animal organs, and it is the method of choice for quantifying drugs and their metabolites in biological fluids. Nevertheless, both instruments have...