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A high‐speed liquid chromatography/tandem mass spectrometry platform using multiplexed multiple‐injection chromatography controlled by single software and its application in discovery ADME screening
Author(s) -
Zhang Jun,
Vath Marianne,
Ferraro Cheryl,
Li Ying,
Murphy Keeley,
Zvyaga Tatyana,
Weller Harold,
Shou Wilson
Publication year - 2013
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.6514
Subject(s) - chemistry , chromatography , bioanalysis , tandem mass spectrometry , software , liquid chromatography–mass spectrometry , adme , mass spectrometry , computer science , in vitro , biochemistry , programming language
RATIONALE Multiplexed liquid chromatography (LC) coupled with multiple‐injection‐chromatogram acquisition has emerged as the method of choice for high‐speed discovery bioanalysis, because it significantly reduces injection‐to‐injection cycle time while maintaining the chromatography quality. Historically, systems utilizing this approach had been custom built, and therefore relied on custom software tools to communicate with multiple vendor software for system control, which lacked transferability, flexibility and robustness. METHODS In this study, we refined a multiplexed bioanalytical system previously reported, by implementing open‐deck auto‐sampler manifold and multiple‐injection‐chromatogram acquisition, all on a commercially available system with single software control. RESULTS As a result of these improvements, the developed LC/tandem mass spectrometry (MS/MS) method on the system was nearly three times faster than the previous method, while demonstrating comparable analytical accuracy, precision and robustness. This system has been evaluated for in vitro ADME screening assays including metabolic stability, CYP inhibition and Caco‐2. The biological data generated on the developed system displayed good correlation with those from the previous LC/MS/MS approaches. CONCLUSIONS The developed platform demonstrated applicability to the in vitro screening assays evaluated and has been successfully implemented to support the high‐throughput metabolic stability assay, with a significantly improved bioanalytical throughput, capacity and data turnaround. Copyright © 2013 John Wiley & Sons, Ltd.