“Head-cut” 2DLC–HRMS (RPLC → HILIC) enhancing non-targeted chemical coverage in environmental exposomics.
Year: 2026
Type: preprint
Abstract: Chemical coverage remains a major limitation in environmental non-target analysis (NTA), as conventional one-dimensional liquid chromatography (1D-LC) provides incomplete retention and separation across the broad physicochemical space encountered in complex samples. Here, we developed an online “head-cut” two-dimensional liquid chromatography–high-resolution tandem mass spectrometry (2DLC–HRMS/MS) approach combining reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC), using a dual-trap system combining porous graphitic carbon and trimodal ion-exchange sorbents, to recover complementary regions of environmental chemical space within a single analysis. Trapping and modulation were first evaluated using a representative set of contaminants of emerging concern (CECs), evidencing that the combined complementary trapping materials achieves quantitative transfer (40-100%) of chemically diverse polar and mobile analytes to HILIC. Feature-based NTA performance of the optimized 2DLC method was comparatively evaluated in river water and effluent wastewater and compared with the corresponding 1D-HILIC and 1D-RPLC. “Head-cut” 2DLC yielded approximately 2.3–2.6-fold more blank-corrected ESI(+) and ESI(−) features than either individual 1D separation. Beyond feature level coverage, DIA componentization demonstrated that precursor-associated MS/MS information increased and successfully distributed across both 2DLC chromatographic domains. Fragment Ambiguity Score (FAS) analysis of ESI(+) data further confirmed the occurrence of low-ambiguity, structurally informative fragments within the expanded separation space. These results demonstrate that wide-interaction recovery of the RPLC blind spot can extend measurable chemical space and access to fragmentation information relevant for structural annotation, supporting “head-cut” RPLC→HILIC–HRMS/MS as a promising strategy for increasing chemical coverage in environmental NTA.
Source: ChemRxiv
Authors: Lapo Renai, Guylain. T. A. Cuiper, Viktoriia Turkina, Aleksandra Chojnacka, Saer Samanipour, Andrea F. G. Gargano
Institution: University of Amsterdam
Language: English
Subfield: Analytical Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Awards: G2252855781, G5691230608
OpenAlex ID: W7215990825