Demonstration of the capabilities of a parallel high performance liquid chromatography tandem mass spectrometry system for use in the analysis of drug discovery plasma samples

There is a continuing need for increased throughput in the evaluation of ne w drug entities in terms of their pharmacokinetic (PK) parameters. This rep ort describes an alternative procedure for increasing the throughput of pla sma samples assayed in one overnight analysis: the use of parallel high per formance liquid chromatography (HPLC) combined with tandem mass spectrometr y (parallel LC/MS/MS), For this work, two HPLC systems were linked so that their combined effluent flowed into one tandem MS system. The parallel HPLC /APCI-MS/MS system consisted of two Waters 2690 Alliance systems (each one included an HPLC pump and an autosampler) and one Finnigan TSQ 7000 triple quadrupole mass spectrometer, Therefore, the simultaneous chromatographic s eparation of the plasma samples was carried out in parallel on two HPLC sys tems. The MS data system was able to deconvolute the data to calculate the results for the samples. Using this system, 20 compounds were tested in one overnight assay using the rapid rat PK screening model which includes a to tal of PO standards plus samples and two solvent blanks per compound tested . This application provides an additional means of increasing throughput in the drug discovery PK assay arena; using this approach a two-fold increase in throughput can be achieved in the assay part of the drug discovery rat PK screening step. Copyright (C) 1999 John Wiley & Sons, Ltd.