Quantitative-Qualitative Data Acquisition Using a Benchtop Orbitrap Mass Spectrometer
Quantitative-Qualitative Data Acquisition Using a Benchtop Orbitrap Mass Spectrometer
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DOI：
10.1016/j.jasms.2009.03.002
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发表时间：
2009-08-01
影响因子：
3.2
通讯作者：
Taylor, Lester
中科院分区：
文献类型：
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作者：
Bateman, Kevin P.;Kellmann, Markus;Taylor, Lester
目前发现阶段药物代谢研究的方法（药代动力学、微粒体稳定性等）通常使用基于三重四极杆的方法进行定量分析。这就需要优化 Q1 和 Q3 m/z 值、碰撞能量和界面电压等参数。这些研究仅检测到特定的化合物，而有关其他成分（例如代谢物）的信息会丢失。执行全扫描采集以进行定量分析的能力将消除对化合物优化的需要，同时能够检测代谢物和其他非药物相关的内源性成分。这样的仪器必须提供适合发现阶段定量研究的灵敏度、选择性、动态范围和扫描速度。在这项研究中，使用基于 Orbitrap 的原型台式质量分析仪从人体微粒体孵化样品以及药代动力学研究中的大鼠血浆中收集定量和定性数据。仪器参数如扫描速度、分辨率和质量准确度将根据定量-定性工作流程的要求进行讨论。讨论了执行高选择性定性分析同时表征体外和体内研究代谢物的能力。 (J Am Soc Mass Spectrom 2009, 20, 1441-1450) (C) 2009 由 Elsevier Inc. 代表美国质谱学会出版
Current approaches to discovery-stage drug metabolism studies (pharmacokinetics, microsomal stability, etc.) typically use triple-quadrupole-based approaches for quantitative analysis. This necessitates the optimization of parameters such as Q1 and Q3 m/z values, collision energy, and interface voltages. These studies detect only the specified compound and information about other components, such as metabolites, is lost. The ability to perform full-scan acquisition for quantitative analysis would eliminate the need for compound optimization while enabling the detection of metabolites and other non-drug-related endogenous components. Such an instrument would have to provide sensitivity, selectivity, dynamic range, and scan speed Suitable for discovery-stage quantitative studies. In this study, a prototype benchtop Orbitrap-based mass analyzer was used to collect both quantitative and qualitative data from human microsomal incubation samples as well as rat plasma from pharmacokinetic studies. Instrumental parameters Such as scan speed, resolution, and mass accuracy are discussed in relation to the requirements for a quantitative-qualitative workflow. The ability to perform highly selective qualitative analysis while simultaneously characterizing metabolites from both in vitro and in vivo studies is discussed. (J Am Soc Mass Spectrom 2009, 20, 1441-1450) (C) 2009 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry