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ViewLux Microplate Imager for Metabolite Profiling: Validation and Applications in Drug Development

Bourgailh, Julien and Garnier, Maxime and Nufer, Robert and Pirard, Hans and Walles, Markus and Swart, Pieter Jacob (2014) ViewLux Microplate Imager for Metabolite Profiling: Validation and Applications in Drug Development. J Anal Bioanal Tech.

Abstract

Generation of early information on metabolic pathways, metabolite structures and their systemic exposure is a highly time consuming activity during the drug development process. Since these data have become of higher interest for the health authorities, efforts have been made to provide results as early as possible. Metabolite profiling using 3H or 14C radiolabeled compounds has been improved in recent years to accelerate this activity, with the introduction of ultra-performance liquid chromatography, coupled with radio-flow detectors or microplate scintillation counters after fraction collection of the eluent flow. ViewLux Ultra HTS is an instrument originally designed for high throughput in biological assays requiring absorbance or fluorescence detections. In this work, we evaluate the capability of the new generation of the instrument for both 14C and 3H detection. One focus in this work is on data processing of the Viewlux, especially the background subtraction in comparison to conventional TopCount instruments, as this has an impact on the limit of detection for samples containing low amounts of radioactivity like samples originating from ADME studies. We demonstrate that the limit of detection can be lowered by prolonging the exposure time for 3H labeled compounds up to 2 h , which still results in a significant time gain compared to conventional TopCount detection.
We validated the ViewLux for our metabolite profiling applications (in vitro and in vivo ADME samples) in early drug development using UPLC followed by fraction collection in 384 well plates and demonstrated for our applications that limits of detection of 2.2 and 24 dpm/ well for 14C and 3H, respectively could be reached. We also demonstrate in this work how endogenous interferences resulting in false positive peaks in samples containing low amounts of radioactivity and how this can be overcome by using customized light filters.
We also discuss how the ViewLux can shorten turnaround times for ADME studies when it is combined with UPLC and automated sample handling devices like the PlateCrane.

Item Type: Article
Keywords: Viewlux, ADME radioactivity detection, metabolite profiling
Date Deposited: 26 Apr 2016 23:46
Last Modified: 26 Apr 2016 23:46
URI: https://oak.novartis.com/id/eprint/21000

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