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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.

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.

Rapid communications in mass spectrometry : RCM (2013-03-16)
Jun Zhang, Marianne Vath, Cheryl Ferraro, Ying Li, Keeley Murphy, Tatyana Zvyaga, Harold Weller, Wilson Shou
摘要

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. 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. 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. 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.

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Sigma-Aldrich
(±)-普萘洛尔 盐酸盐, ≥99% (TLC), powder
Supelco
盐酸普萘洛尔, Pharmaceutical Secondary Standard; Certified Reference Material
普萘洛尔 盐酸盐, European Pharmacopoeia (EP) Reference Standard
Supelco
Propranolol hydrochloride solution, 1.0 mg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®