Matrix Effect Compensation in Small-Molecule Profiling for an LC–TOF Platform Using Multicomponent Postcolumn Infusion,Analytical Chemistry

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Matrix Effect Compensation in Small-Molecule Profiling for an LC–TOF Platform Using Multicomponent Postcolumn Infusion
Analytical Chemistry ( IF 6.7 ) Pub Date : 2015-05-27 00:00:00 , DOI: 10.1021/ac504268y
Oskar González _{1,

2} , Michael van Vliet ₁ , Carola W. N. Damen ₁ , Frans M. van der Kloet ₁ , Rob J. Vreeken ₁ , Thomas Hankemeier ₁

Affiliation

The possible presence of matrix effect is one of the main concerns in liquid chromatography–mass spectrometry (LC–MS)-driven bioanalysis due to its impact on the reliability of the obtained quantitative results. Here we propose an approach to correct for the matrix effect in LC–MS with electrospray ionization using postcolumn infusion of eight internal standards (PCI-IS). We applied this approach to a generic ultraperformance liquid chromatography–time-of-flight (UHPLC–TOF) platform developed for small-molecule profiling with a main focus on drugs. Different urine samples were spiked with 19 drugs with different physicochemical properties and analyzed in order to study matrix effect (in absolute and relative terms). Furthermore, calibration curves for each analyte were constructed and quality control samples at different concentration levels were analyzed to check the applicability of this approach in quantitative analysis. The matrix effect profiles of the PCI-ISs were different: this confirms that the matrix effect is compound-dependent, and therefore the most suitable PCI-IS has to be chosen for each analyte. Chromatograms were reconstructed using analyte and PCI-IS responses, which were used to develop an optimized method which compensates for variation in ionization efficiency. The approach presented here improved the results in terms of matrix effect dramatically. Furthermore, calibration curves of higher quality are obtained, dynamic range is enhanced, and accuracy and precision of QC samples is increased. The use of PCI-ISs is a very promising step toward an analytical platform free of matrix effect, which can make LC–MS analysis even more successful, adding a higher reliability in quantification to its intrinsic high sensitivity and selectivity.

中文翻译：

使用多组分柱后注入的LC–TOF平台小分子分析中的基质效应补偿

基质效应的可能存在是液相色谱-质谱（LC-MS）驱动的生物分析中的主要问题之一，因为它对获得的定量结果的可靠性有影响。在这里，我们提出了一种方法，该方法通过使用八种内标（PCI-IS）的柱后注入电喷雾电离来校正LC-MS中的基质效应。我们将此方法应用于为小分子分析开发的通用超高性能液相色谱-飞行时间（UHPLC-TOF）平台，主要侧重于药物。不同尿液样本中掺入了19种具有不同理化性质的药物，并进行了分析，以研究基质效应（绝对和相对）。此外，构建每种分析物的校准曲线，并分析不同浓度水平的质量控制样品，以检查该方法在定量分析中的适用性。PCI-IS的基质效应谱是不同的：这证实了基质效应是化合物依赖性的，因此必须为每种分析物选择最合适的PCI-IS。使用分析物和PCI-IS响应重建色谱图，这些响应图用于开发一种可补偿电离效率变化的优化方法。此处介绍的方法在矩阵效应方面显着改善了结果。此外，获得了更高质量的校准曲线，增强了动态范围，并提高了质控样品的准确性和精密度。

更新日期：2015-05-27

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