Whalen Kevin, Gobey Jason, Janiszewski John
Pfizer Global Research and Development, Groton Laboratories, Pfizer Inc., Eastern Point Rd., Groton, CT 06340, USA.
Rapid Commun Mass Spectrom. 2006;20(10):1497-503. doi: 10.1002/rcm.2469.
A centralized approach to acquisition and dissemination of tandem mass spectrometry (MS/MS) conditions within an ADME-screening bioanalytical mass spectrometry group has been developed. The method development process uses two automated software products (Autoscan and Automaton) specifically designed for mass spectrometers manufactured by MDS Sciex. Both provide the ability to quickly determine selected reaction monitoring (SRM) transitions for hundreds of compounds per day. In addition, Autoscan determines optimal polarity and collision energy (CE). Automaton also determines the optimal declustering potential (DP) as well as the CE. The resulting optimized conditions are loaded into a central database for access by LC/MS/MS bioanalysis workstations in the group. The effect of DP and CE on the sensitivity was investigated. Optimization of DP improved signal response about 27% on average. For approximately 10% of compounds, signal enhancement was greater than 50% compared to the generic setting. A generic setting of DP = 25 V can be used for the majority of ADME-screening applications. Optimization of CE can have a much larger impact on signal intensity and a minimum of three CE settings should be tested. We have determined that CE values of 1, 30 and 45 V provide adequate coverage for most small molecule drug discovery analytes.
在一个药物代谢动力学（ADME）筛选生物分析质谱组内，已经开发出一种集中式获取和传播串联质谱（MS/MS）条件的方法。方法开发过程使用了两款专门为 MDS Sciex 制造的质谱仪设计的自动化软件产品（Autoscan 和 Automaton）。这两款软件都具备每天快速确定数百种化合物的选择反应监测（SRM）跃迁的能力。此外，Autoscan 能确定最佳极性和碰撞能量（CE）。Automaton 还能确定最佳去簇电位（DP）以及 CE。最终得到的优化条件被载入中央数据库，供该组的液相色谱/串联质谱生物分析工作站访问。研究了 DP 和 CE 对灵敏度的影响。DP 的优化平均使信号响应提高了约 27%。对于大约 10%的化合物，与通用设置相比，信号增强超过了 50%。DP = 25 V 的通用设置可用于大多数 ADME 筛选应用。CE 的优化对信号强度的影响可能更大，应至少测试三个 CE 设置。我们已经确定，1、30 和 45 V 的 CE 值能为大多数小分子药物发现分析物提供足够的覆盖范围。
