Cassette-accelerated rapid rat screen: a systematic procedure for the dosing and liquid chromatography/atmospheric pressure ionization tandem mass spectrometric analysis of new chemical entities as part of new drug discovery

This report addresses the continuing need for increased throughput in the e valuation of new chemical entities (NCEs) in terms of their pharmacokinetic (PK) parameters by describing an alternative procedure for increasing the throughput of the in vivo screening of NCEs in the oral rat PK model. The n ew approach is called 'cassette-accelerated rapid rat screen' (CARRS). In t his assay, NCEs are dosed individually (n = 2 rats/compound) in batches of six compounds per set. The assay makes use of a semi-automated protein prec ipitation procedure for sample preparation in a 96-well plate format. The l iquid chromatography/atmospheric pressure ionization tandem mass spectromet ry (LC/API-MS/MS) assay is also streamlined by analyzing the samples as 'ca ssettes of six'. Using this new approach, a threefold increase in throughpu t was achieved over the previously reported 'rapid rat screen'. Copyright ( C) 2001 John Wiley & Sons, Ltd.