Korfmacher W A, Cox K A, Ng K J, Veals J, Hsieh Y, Wainhaus S, Broske L, Prelusky D, Nomeir A, White R E
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, 2015 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
Rapid Commun Mass Spectrom. 2001;15(5):335-40. doi: 10.1002/rcm.235.
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".
本报告通过描述一种替代程序，以提高口服大鼠药代动力学（PK）模型中新型化学实体（NCEs）体内筛选的通量，来满足持续增长的对提高NCEs药代动力学参数评估通量的需求。这种新方法称为“盒式加速快速大鼠筛选”（CARRS）。在该试验中，NCEs以每组六个化合物为一批进行单独给药（每组化合物n = 2只大鼠）。该试验利用半自动蛋白沉淀程序，以96孔板形式进行样品制备。液相色谱/大气压电离串联质谱（LC/API-MS/MS）试验也通过将样品作为“六个一组”进行分析而得以简化。使用这种新方法，通量比先前报道的“快速大鼠筛选”提高了两倍。
