High-Throughput Microsomal Stability Assay for Screening New Chemical Entities in Drug Discovery
High-Throughput Microsomal Stability Assay for Screening New Chemical Entities in Drug Discovery
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DOI：
10.1177/1087057108323911
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发表时间：
2008-10-01
影响因子：
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通讯作者：
Mionteagudo, Edith
中科院分区：
文献类型：
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作者：
Fonsi, Massimiliano;Orsale, Maria V.;Mionteagudo, Edith
在这项工作中，作者提出了一种新的，机器人，自动化的协议，用于评估代谢稳定性协议组装油的汉密尔顿平台和一个新的策略，合并样本（盒分析）。为了提高液相色谱（LC）步骤的高通量，还开发了快速色谱和自动液相色谱串联质谱（LC/MS/MS）分析方法。并生成快速数据分析系统，其将通过LC/MS/MS获得的峰面积转换为固有清除率值。对微粒体稳定性试验的所有步骤进行了仔细研究和优化。测量间隙的标准误差和置信区间也在该过程中自动生成，以允许对观察值的显著性进行所有即时评价。将基于2种和4种不同分析物的合并分析的方法与不合并的标准方法进行比较。一个简单的统计处理方法可以用来证明它们的等效性。在准确性和高通量能力之间的最佳折衷方面，分析了开发的不同协议。（Journal of Biomolecular Screening 2008：862 - 869）
In this work, the authors present a novel, robotic, automated protocol for assessing a metabolic stability protocol assembled oil a Hamilton platform and a new strategy for pooling samples (cassette analysis). To increase the high throughput of the liquid chromatography (LC) step, fast chromatography and automated liquid chromatography tandem mass spectrometry (LC/MS/MS) analytical methods were also developed. and a rapid data analysis system was generated that converts peak areas obtained by LC/MS/MS in intrinsic clearance values. All of the steps of the microsomal stability assay were carefully studied and optimized. Standard errors and confidence intervals of the measured clearances were also automatically generated in the process to allow ail immediate evaluation of the significance of observed values. Methods based on pooling analysis of 2 and 4 different analytes were compared with a standard method without pooling. A simple statistical treatment wits used to show their equivalence. The different protocols developed were analyzed in terms of the best compromise between accuracy and high-throughput capabilities. (Journal of Biomolecular Screening 2008:862-869)