Application of a rapid and integrated analysis system (RIAS) as a high-throughput processing tool for in vitro ADME samples by liquid chromatography/tandem mass spectrometry
| Autor: | Thomas Arnhold, Andreas H. Luippold, Roderich D. Süssmuth, Wolfgang Jörg, Beate Krüger |
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| Rok vydání: | 2011 |
| Předmět: |
Chromatography
Chemistry Drug Evaluation Preclinical Tandem mass spectrometry Biochemistry Analytical Chemistry High-Throughput Screening Assays Systems Integration Fully automated Pharmaceutical Preparations Liquid chromatography–mass spectrometry Tandem Mass Spectrometry ddc:570 Molecular Medicine Humans Caco-2 Cells Throughput (business) Software Biotechnology ADME Chromatography Liquid |
| Zdroj: | Journal of biomolecular screening. 16(3) |
| ISSN: | 1552-454X |
| Popis: | Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich. This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. Over the past decade, drug discovery programs have started to address the optimization of key ADME properties already at an early stage of the process. Hence, analytical chemists have been confronted with tremendously rising sample numbers and have had to develop methodologies accelerating quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS). This article focuses on the application of a generic and fully automated LC/MS/MS, named Rapid and Integrated Analysis System (RIAS), as a high-throughput platform for the rapid quantification of drug-like compounds in various in vitro ADME assays. Previous efforts were dedicated to the setup and feasibility study of a workflow-integrated platform combining a modified high-throughput liquid handling LC/MS/MS system controlled by a customized software interface and a customized data-processing and reporting tool. Herein the authors present an extension of this previously developed basic application to a broad set of ADME screening campaigns, covering CYP inhibition, Caco-2, and PAMPA assays. The platform is capable of switching automatically between various ADME assays, performs MS compound optimization if required, and provides a speed of 8 s from sample to sample, independently of the type of ADME assay. Quantification and peak review are adopted to the high-throughput environment and tested against a standard HPLC-ESI technology. |
| Databáze: | OpenAIRE |
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