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在液相色谱-串联质谱生物分析中,在保持通量的同时最小化基质效应。

Minimizing matrix effects while preserving throughput in LC-MS/MS bioanalysis.

作者信息

Ye Zhengqi, Tsao Hong, Gao Hong, Brummel Christopher L

机构信息

Drug Innovation Pharmacokinetics, Vertex Pharmaceuticals Inc., Cambridge, MA 02139, USA.

出版信息

Bioanalysis. 2011 Jul;3(14):1587-601. doi: 10.4155/bio.11.141.

Abstract

BACKGROUND

Phospholipids are known to cause matrix effects in LC-MS analysis and are not effectively removed by one of the most common method of sample preparation: organic solvent protein precipitation. The objective of this research is to minimize phospholipid interferences chromatographically.

RESULTS

In this article we examine several chromatographic approaches and highlight the method we developed that allows for the rapid gradient separation of model drug molecules from phospholipids.

CONCLUSION

The new approach (which utilizes a mixture of methanol and acetonitrile as the organic mobile phase on a 2.1 × 20 mm C18 column) minimized phospholipids-related matrix effects in the analysis of plasma samples prepared by protein precipitation and is suitable for high-throughput bioanalysis in drug discovery.

摘要

背景

已知磷脂会在液相色谱 - 质谱分析中引起基质效应,并且通过最常用的样品制备方法之一:有机溶剂蛋白沉淀法无法有效去除。本研究的目的是通过色谱法将磷脂干扰降至最低。

结果

在本文中,我们研究了几种色谱方法,并重点介绍了我们开发的一种方法,该方法能够实现模型药物分子与磷脂的快速梯度分离。

结论

新方法(在2.1×20 mm C18柱上使用甲醇和乙腈的混合物作为有机流动相)在分析通过蛋白沉淀制备的血浆样品时,将与磷脂相关的基质效应降至最低,适用于药物发现中的高通量生物分析。

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