Premium
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
Author(s) -
Korfmacher Walter A.,
Cox Kathleen A.,
Ng Kwokei J.,
Veals John,
Hsieh Yunsheng,
Wainhaus Sam,
Broske Lisa,
Prelusky Dan,
Nomeir Amin,
White Ronald E.
Publication year - 2001
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.235
Subject(s) - chemistry , chromatography , protein precipitation , atmospheric pressure chemical ionization , liquid chromatography–mass spectrometry , tandem mass spectrometry , mass spectrometry , drug discovery , throughput , tandem , chemical ionization , sample preparation , pharmacokinetics , ionization , pharmacology , organic chemistry , biochemistry , medicine , ion , telecommunications , materials science , wireless , composite material , computer science
Abstract This report addresses the continuing need for increased throughput in the evaluation 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 new approach is called ‘cassette‐accelerated rapid rat screen’ (CARRS). In this 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 precipitation procedure for sample preparation in a 96‐well plate format. The liquid chromatography/atmospheric pressure ionization tandem mass spectrometry (LC/API‐MS/MS) assay is also streamlined by analyzing the samples as ‘cassettes of six’. Using this new approach, a threefold increase in throughput was achieved over the previously reported ‘rapid rat screen’. Copyright © 2001 John Wiley & Sons, Ltd.