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Higher‐throughput screening for Caco‐2 permeability utilizing a multiple sprayer liquid chromatography/tandem mass spectrometry system
Author(s) -
Fung Eliza N.,
Chu Inhou,
Li Cheng,
Liu Tongtong,
Soares Anthony,
Morrison Richard,
Nomeir Amin A.
Publication year - 2003
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.1165
Subject(s) - chemistry , chromatography , mass spectrometry , liquid chromatography–mass spectrometry , tandem mass spectrometry , throughput , electrospray , process engineering , computer science , telecommunications , engineering , wireless
In the current drug discovery environment, higher‐throughput analytical assays have become essential to keep pace with the screening demands for drug metabolism and pharmacokinetics (DMPK) attributes. This has been dictated by advances primarily in chemical procedures, notably combinatorial and parallel syntheses, which has resulted in many‐fold increases in the number of compounds requiring DMPK evaluation. Because of its speed and specificity, liquid chromatography/tandem mass spectrometry (LC/MS/MS) has become the dominant technology for sample analysis in the DMPK screening assays. For higher‐throughput assays, analytical speed as well as other factors such as method development, data processing, quality control, and report generation, must be optimized. The four‐way multiplexed electrospray interface (MUX®), which allows for the analysis of four LC eluents simultaneously, has been adopted to maximize the rate of sample introduction into the mass spectrometer. Generic fast‐gradient HPLC methods that are suitable for approximately 80% of the new chemical entities encountered have been developed. In‐house‐written software programs have been used to streamline information flow within the system, and for quality control by automatically identifying analytical anomalies. By integrating these components together with automated method development and data processing, a system capable of screening 100 compounds per week for Caco‐2 permeability has been established. Copyright © 2003 John Wiley & Sons, Ltd.