To close the “analytical gap” in the liquid chromatographic (LC) analysis of highly polar substances, two techniques which have been suggested earlier were tested in terms of retention factors and detection limits: hydrophilic interaction liquid chromatography (HILIC) and mixed-mode chromatography (MMC). A substance mix of 55 analytes ranging from logD − 8.2 to 3.4 and 17 different LC columns, also comprising additional reversed-phase columns were used. Contrary to most reversed-phase columns, column bleed has been identified as an important factor, which may cause serious restrictions during high-resolution mass spectrometric detection (HRMS). We found that highly abundant background masses continuously eluting from the columns heavily influence ion transmission to the detector. As a result, the linear dynamic range as well as the sensitivity decreases and thus limits the HRMS applicability of some columns. We therefore recommend a thorough investigation of ion transmission during HRMS method development. This will help to maintain the high potential of HRMS in terms of qualitative and quantitative screening analysis.

为了弥补高极性物质在液相色谱（LC）分析中的“分析空白”，对两种较早提出的技术进行了保留因子和检测限方面的测试：亲水相互作用液相色谱（HILIC）和混合模式色谱（MMC）。55种分析物的物质混合物，范围从log D−使用了8.2至3.4和17种不同的LC色谱柱，其中还包括其他反相色谱柱。与大多数反相色谱柱相反，色谱柱流失已被认为是重要因素，它可能在高分辨率质谱检测（HRMS）期间造成严重限制。我们发现，连续不断地从色谱柱上洗脱下来的高度丰富的背景质量严重影响了离子向检测器的传输。结果，线性动态范围以及灵敏度降低，从而限制了某些色谱柱的HRMS适用性。因此，我们建议对HRMS方法开发过程中的离子传输进行彻底的研究。这将有助于在定性和定量筛选分析方面保持HRMS的高潜力。