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Liquid chromatography/tandem mass spectrometric quantification with metabolite screening as a strategy to enhance the early drug discovery process
Author(s) -
Tiller Philip R.,
Romanyshyn Leslie A.
Publication year - 2002
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.708
Subject(s) - chemistry , chromatography , metabolite , drug discovery , tandem mass spectrometry , tandem , high performance liquid chromatography , mass spectrometry , throughput , computer science , telecommunications , biochemistry , materials science , composite material , wireless
Throughput for early discovery drug metabolism studies can be increased with the concomitant acquisition of metabolite screening information and quantitative analysis using ultra‐fast gradient chromatographic methods. Typical ultra‐fast high‐performance liquid chromatography (HPLC) parameters used during early discovery pharmacokinetic (PK) studies, for example, employ full‐linear gradients over 1–2 min at very high flow rates (1.5–2 mL/min) on very short HPLC columns (2 × 20 mm). These conditions increase sample throughput by reducing analytical run time without sacrificing chromatographic integrity and may be used to analyze samples generated from a variety of in vitro and in vivo studies. This approach allows acquisition of more information about a lead candidate while maintaining rapid analytical turn‐around time. Some examples of this approach are discussed in further detail. Copyright © 2002 John Wiley & Sons, Ltd.