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.
J Biomol Screen
; 16(3): 370-7, 2011 Mar.
Article
en En
| MEDLINE
| ID: mdl-21335598
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cromatografía Liquida
/
Evaluación Preclínica de Medicamentos
/
Espectrometría de Masas en Tándem
/
Ensayos Analíticos de Alto Rendimiento
Límite:
Humans
Idioma:
En
Revista:
J Biomol Screen
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2011
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Estados Unidos