Matrix effects are probably the Achilles heel of most quantitative liquid chromatography mass spectrometry (LC–MS) methods based on electrospray ionization. This work reports the evaluation of matrix effects in challenging matrices such as food extracts, human urine or wastewater at different dilution factors using nanoflow liquid chromatography-high resolution mass spectrometry (LC–MS). For this purpose, a suite of representative low-molecular weight compounds such as pesticides, drugs of abuse, sport drugs or environmental contaminants were selected. The approach is based on the use of reversed-phase C18 nano columns furnished with an integrated emitter tip. The nanoflow LC system was combined with full-scan high resolution mass spectrometry using a HRMS (orbitrap) instrument operated at a resolution of 70000. The sensitivity achieved with this configuration enables the implementation of high dilution factors (e.g. 1:20, 1:50 or beyond). When combining nanoflow LC–MS analysis with such high dilution factors (e.g. 1:50), signal suppression was negligible in most cases, so that matrix-matched standards may eventually be skipped, simplifying laboratory workflows by using external calibration in demanding applications such as drug analysis in urine, environmental contaminants in wastewater or pesticide testing in food, thus, eliminating the need for standard addition, matrix-matched calibration or isotopically-labelled standards.

基质效应可能是大多数基于电喷雾电离的定量液相色谱质谱法（LC-MS）的致命弱点。这项工作报告了使用纳流液相色谱-高分辨率质谱（LC-MS）对不同稀释因子下的挑战性基质（如食品提取物，人尿或废水）中基质效应的评估。为此，选择了一组代表性的低分子量化合物，例如农药，滥用药物，运动药物或环境污染物。该方法基于使用配备有集成发射器尖端的反相C18纳米柱。使用以70000分辨率运行的HRMS（orbitrap）仪器，将纳流LC系统与全扫描高分辨率质谱仪结合使用。通过这种配置实现的灵敏度使得可以实现高稀释倍数（例如1：20、1：50或更高）。当将纳流LC-MS分析与如此高的稀释倍数（例如1:50）结合使用时，在大多数情况下，信号抑制作用可以忽略不计，因此最终可以跳过基质匹配的标准品，通过在要求苛刻的应用中使用外部校准来简化实验室工作流程，例如尿液中的药物分析，废水中的环境污染物或食品中的农药检测，因此无需标准添加，基质匹配的校准或同位素标记的标准。