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

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. Histori...

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Bibliographic Details
Published in:Rapid communications in mass spectrometry 2013-04, Vol.27 (7), p.731-737
Main Authors: Zhang, Jun, Vath, Marianne, Ferraro, Cheryl, Li, Ying, Murphy, Keeley, Zvyaga, Tatyana, Weller, Harold, Shou, Wilson
Format: Article
Language:English
Subjects:
Animals
Assaying
Caco-2 Cells
Chromatography, Liquid - instrumentation
Chromatography, Liquid - methods
Computer programs
Cytochrome P-450 CYP3A - analysis
Cytochrome P-450 CYP3A - metabolism
Drug Discovery - methods
Humans
In vitro testing
Linear Models
Liquid chromatography
Mass spectrometry
Mice
Models, Chemical
Multiplexing
Propranolol - analysis
Propranolol - chemistry
Rats
Reproducibility of Results
Screening
Software
Tandem Mass Spectrometry - methods
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Summary: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.
ISSN:0951-4198
1097-0231
DOI:10.1002/rcm.6514