“Head-cut” 2DLC–HRMS (RPLC → HILIC) enhancing non-targeted chemical coverage in environmental exposomics.
5 affiliations
- 1Van ‘t Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam, 1090 GD, Amsterdam, Netherlands
- 2Life Sciences & Chemistry
- 3Queensland Alliance for Environmental Health Sciences (QAEHS, 20 Cornwall Street, Woolloongabba, QLD, Australia, 4102
- 4UvA Data Science Center
- 5University of Amsterdam
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.
Related
- From Sampling to Screening: A Review of Targeted and Non-Targeted PFAS Analysis in Environmental Samples
- Targeted Chemical Functionalization of the Amorphous Phase in Polyolefins via Controlled Solvent Swelling.
- Counterfactual explanation-based targeted regulation of key chemical indicators for improving tobacco leaf sensory quality
- Beyond nitrogen: an oxygen-chemical-potential framework for defect-engineered TiO₂ nanotube architectures in energy conversion and environmental catalysis.
- From Promotion to Poisoning: Temperature- and Coverage-Dependent Effects of Trace Fe on the Hydrogen Evolution Activity of Pt
BibTeX
@misc{renai2026headcut,
title = {{“Head-cut” 2DLC–HRMS (RPLC → HILIC) enhancing non-targeted chemical coverage in environmental exposomics.}},
author = {Lapo Renai and Guylain. T. A. Cuiper and Viktoriia Turkina and Aleksandra Chojnacka and Saer Samanipour and Andrea F. G. Gargano},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15009781/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009781/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - “Head-cut” 2DLC–HRMS (RPLC → HILIC) enhancing non-targeted chemical coverage in environmental exposomics.
AU - Lapo Renai
AU - Guylain. T. A. Cuiper
AU - Viktoriia Turkina
AU - Aleksandra Chojnacka
AU - Saer Samanipour
AU - Andrea F. G. Gargano
PY - 2026
DA - 2026/10/02
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009781/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009781/v1
AB - 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.
ER -