Investigation of matrix effects in bioanalytical high-performance liquid chromatography/tandem mass spectrometric assays: application to drug discovery
Investigation of matrix effects in bioanalytical high-performance liquid chromatography/tandem mass spectrometric assays: application to drug discovery
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DOI：
10.1002/rcm.876
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发表时间：
2003-01-01
影响因子：
2
通讯作者：
Korfmacher, WA
中科院分区：
文献类型：
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作者：
Mei, H;Hsieh, YS;Korfmacher, WA
对生物分析用高效液相色谱/串联质谱（HPLC/MS/MS）分析中基质效应（“离子抑制”或“离子增强”）的原因进行了一系列研究。先前的研究已经报道，基质效应主要是由于生物流体中的内源性组分，并且对于电喷雾电离（ESI）比对于大气压化学电离（APCI）更关注。在本报告中，我们证明：（1）基质效应也可以由外源性材料引起，例如不同品牌的塑料管中含有的聚合物，或常用的抗凝剂肝素锂;（2）基质效应不仅是电离模式（PCI或ESI）相关，但也包括源设计（Sciex，Finnigan，Micromass）依赖;（3）对于至少一个供应商的设计，我们发现APCI模式比ESI模式对基质效应更敏感。基于这些发现，我们提出了以下避免基质效应的简单策略：（1）选择相同品牌的塑料管用于处理和储存血浆样品和加标血浆标准品;（2）避免使用肝素锂作为抗凝剂;（3）当遇到基质效应时，尝试切换电离模式或切换到不同的质谱仪。这三种策略使我们能够使用蛋白质沉淀和通用快速LC技术来生成可靠的LC/MS/MS数据，以支持早期药物发现阶段的药代动力学研究。版权所有（C）2002约翰威利父子有限公司
A series of studies was performed to investigate some of the causes for matrix effects ('ion suppression' or 'ion enhancement') in bioanalytical high-performance liquid chromatography/ tandem mass spectrometry (HPLC/MS/MS) asays. Previous studies have reported that matrix effects are mainly due to endogenous components in biological fluids and are a greater concern for electrospray ionization (ESI) than for atmospheric pressure chemical ionization (APCI). In this report we demonstrate that: (1) matrix effects can also be caused by exogenous materials, such as polymers contained in different brands of plastic tubes, or Li-heparin, a commonly used anticoagulant; (2) matrix effects are not only ionization mode (A PCI or ESI) dependent, but also source design (Sciex, Finnigan, Micromass) dependent; and (3) for at least one vendor's design, we found the APCI mode to be more sensitive to matrix effects than the ESI mode. Based on these findings, we have proposed the following simple strategies to avoid matrix effects: (1) select the same brand of plastic tubes for processing and storing plasma samples and spiked plasma standards; (2) avoid using Li-heparin as the anticoagulant; and (3) try switching the ionization mode or switching to different mass spectrometers when matrix effects are encountered. These three strategies have allowed us to use protein precipitation and generic fast LC techniques to generate reliable LC/MS/MS data for the support of pharmacokinetic studies at the early drug discovery stage. Copyright (C) 2002 John Wiley Sons, Ltd.