使用高分辨飞行时间质谱仪的新型超快速代谢稳定性分析方法的实施

Implementation of a novel ultra fast metabolic stability analysis method using exact mass TOF-MS.

作者信息

Manna Joseph D, Richardson Samantha J, Moghaddam Mehran F

机构信息

Department of Drug Metabolism & Pharmacokinetics, Celgene Corporation, 10300 Campus Point Dr., San Diego, CA 92121, USA.

出版信息

Bioanalysis. 2017 Feb;9(4):359-368. doi: 10.4155/bio-2016-0187. Epub 2017 Jan 11.

DOI:10.4155/bio-2016-0187

PMID:28074669

Abstract

AIM

Increasing numbers of compounds requiring stability data means highly optimized methods capable of rapid turnaround are desirable during early discovery. Materials and methods/results: An advanced, generic analytical workflow for metabolic stability has been developed that utilizing ballistic gradient LC (sub 1 min run times), exact mass TOF-MS (Waters Xevo-G2-XS Q-TOF) and automated data processing (Waters UNIFI software) allowed for rapid integration and interpretation of all data produced, eliminating the need for method development and manual processing. We can analyze and process 96 compounds across two species in quadruplicate in a 24-h period with no method development.

CONCLUSION

An advanced bioanalytical workflow has increased our capacity threefold and reduced our instrument/processing needs threefold.

摘要

目的

需要稳定性数据的化合物数量不断增加，这意味着在早期发现阶段需要能够快速周转的高度优化方法。材料与方法/结果：已开发出一种先进的、通用的代谢稳定性分析工作流程，该流程利用快速梯度液相色谱（运行时间不到1分钟）、高分辨飞行时间质谱（沃特世Xevo-G2-XS Q-TOF）和自动化数据处理（沃特世UNIFI软件），能够快速整合和解释所有产生的数据，无需方法开发和手动处理。我们可以在24小时内对两个物种的96种化合物进行一式四份的分析和处理，且无需方法开发。