Ion suppression effects in liquid chromatography-electrospray-ionisation transport-region collision induced dissociation mass spectrometry with different serum extraction methods for systematic toxicological analysis with mass spectra libraries
Ion suppression effects in liquid chromatography-electrospray-ionisation transport-region collision induced dissociation mass spectrometry with different serum extraction methods for systematic toxicological analysis with mass spectra libraries
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DOI：
10.1016/s1570-0232(02)00142-3
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发表时间：
2002-06-15
影响因子：
3
通讯作者：
Weinmann, W
中科院分区：
文献类型：
--
作者：
Müller, C;Schäfer, P;Weinmann, W
研究了血清电喷雾电离质谱（ESI-MS）中不同样品制备方法对离子抑制的影响。本课题是重要的系统毒理学分析，LC-ESI-MS已开发与运输区碰撞诱导解离（ECI-CID）和质谱库搜索。采用连续柱后输注两种供试化合物-可待因和格拉非宁，研究了标准液-液萃取、混合模式固相萃取（SPE）法、蛋白质沉淀法和沉淀与聚合物混合模式SPE相结合法对生物基质离子的抑制作用。可待因（[M+H]（+），m/z 300）和格拉非宁（[M-H]（-），m/z 371）的提取离子色谱图用于监测离子抑制。可待因和格拉非宁的严重离子抑制效应分别在正离子化模式和负离子化模式中检测到，在用SPE（酸性/中性馏分）和蛋白质沉淀以及与SPE结合的蛋白质沉淀进行血清净化后的LC-前峰中。用液-液萃取法检测血清样品，发现阳性模式下可待因的离子抑制较小。在两种电离模式下，混合模式SPE的第二部分（使用RP-C-8和阳离子交换相）均未检测到离子抑制。所有抑制作用都是由提取和/或蛋白质沉淀后存在的极性和未保留的基质成分引起的。然而，在整个梯度中洗脱极性LC前沿后，未观察到特异性离子抑制。可以证明，当使用具有相当长梯度程序的反相HPLC时，离子抑制通常不存在于任何保留时间，但在高通量LC-MS分析的情况下，当分析物未与LC-前端分离时，或在没有色谱分离的流动注射分析中，离子抑制可能发挥重要作用。(C)2002 Elsevier Science B. V.保留所有权利。
Ion suppression effects during electrospray-ionsation mass spectrometry (ESI-MS) caused by different sample preparation procedures for serum were investigated. This topic is of importance for systematic toxicological analysis for which LC-ESI-MS has been developed with transport-region collision-induced dissociation (ECI-CID) and mass spectra library searching. With continuous postcolumn infusion of two test compounds-codeine and glafenine-the ion suppression effects of extracted biological matrix obtained after a standard liquid-liquid extraction, a mixed-mode solid-phase extraction (SPE) method, a protein precipitation method and a combination of precipitation with polymer-based mixed-mode SPE have been investigated. Extracted ion chromatograms of codeine ([M+H](+), m/z 300) and glafenine ([M-H](-), m/z 371) were used for monitoring ion suppression. Severe ion suppression effects for codeine and glafenine were detected in positive and in negative ionisation modes, respectively, in the LC-front peak after serum clean-up with SPE (acid/neutral fraction) and protein precipitation as well as with protein precipitation combined with SPE. Less ion suppression of codeine in positive mode was found with liquid-liquid extraction of serum samples. No ion suppression was detected with the second fraction of the mixed-mode SPE (using RP-C-8 and cation-exchange phase) in both ionisation modes. All suppression effects were caused by polar and unretained matrix components, which were present after extraction and/or protein precipitation. However, no specific ion suppression was seen after elution of the polar LC-front throughout the whole gradient. It could be demonstrated, that ion suppression is not generally present at any retention time when using reversed-phase HPLC with rather long gradient programs, but may play an important role in case of high-throughput LC-MS analysis, when the analyte is not separated from the LC-front, or in flow injection analysis without chromatographic separation. (C) 2002 Elsevier Science B.V. All rights reserved.