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将常规定量/定性方法引入药物代谢动力学(DMPK)研究:经验与发展策略

Introduction of a routine quan/qual approach into research DMPK: experiences and evolving strategies.

作者信息

King Lloyd, Kotian Apoorva, Jairaj Mark

机构信息

DMPK, UCB, 216 Bath Road, Slough, Berks SL1 3WE, UK.

出版信息

Bioanalysis. 2014;6(24):3337-48. doi: 10.4155/bio.14.233.

DOI:10.4155/bio.14.233
PMID:25534790
Abstract

After graduating with an Oceanography degree from Swansea University, Lloyd has spent over 20 years in the field of bioanalysis and metabolite profiling. He started his career in large pharma at Wyeth UK, where he was involved in setting up the first GC and LC-MS/MS systems for both QC and early DMPK assays, employing EI/CI, thermospray, and the then new electrospray ionization techniques. Lloyd then joined Celltech, now UCB, where he is primarily tasked with metabolite profiling by LC-MS and NMR to support both early research projects and late-stage clinical studies. The application of liquid chromatography high-resolution mass spectrometry for simultaneous quantitative and qualitative (quan/qual) analysis has gained momentum across a range of different scientific arenas in recent years. The ability to acquire high quality quantitative data, whilst also capturing qualitative data for either parallel or retrospective analysis, is a powerful resource, especially in view of ever-reducing cycle times, laboratory space and budgets. The quan/qual approach employing a Q-Exactive™ Orbitrap high-resolution mass spectrometer has been successfully introduced into UCB's research DMPK department. This article describes our experiences in introducing quan/qual, issues that we discovered in establishing this new working paradigm, the evolution of the strategy and its future potential.

摘要

劳埃德从斯旺西大学海洋学专业毕业后,已在生物分析和代谢物谱分析领域工作了20多年。他的职业生涯始于惠氏英国公司,在那里他参与建立了用于质量控制和早期药物代谢动力学(DMPK)分析的首批气相色谱和液相色谱-串联质谱(LC-MS/MS)系统,采用电子轰击/化学电离(EI/CI)、热喷雾以及当时新出现的电喷雾电离技术。劳埃德随后加入了现在的优时比公司(原Celltech),他的主要任务是通过液相色谱-质谱联用(LC-MS)和核磁共振(NMR)进行代谢物谱分析,以支持早期研究项目和后期临床研究。近年来,液相色谱高分辨率质谱用于同时进行定量和定性(quan/qual)分析在一系列不同的科学领域得到了广泛应用。能够获取高质量的定量数据,同时还能采集用于平行或回顾性分析的定性数据,是一种强大的资源,尤其是考虑到周期时间、实验室空间和预算不断减少的情况。采用Q-Exactive™ 轨道阱高分辨率质谱仪的quan/qual方法已成功引入优时比公司的研究DMPK部门。本文描述了我们在引入quan/qual方面的经验、在建立这种新工作模式过程中发现的问题、该策略的演变及其未来潜力。

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