Integrating the lactulose-mannitol test for intestinal permeability with untargeted metabolomics for drug monitoring through dual liquid chromatography-mass spectrometry

• DOI: 10.1007/s00216-025-05790-7
• Publication Date: 2025-02-28T15:10:03Z
• Authors: Felina Hildebrand; Cemre Cukaci; Harald Schoeny; Christoph Baumgar...; Bruno Stelzer; Matteo Spedicato; Tobias Frey; Martina Catani; Klaus Schmetterer; Richard Frey; Gunda Koellensperger
• Keywords: Lactulose; Intestinal Permeability

In this study, we developed a customized high-resolution mass spectrometry metabolomics workflow integrating the dual sugar test employing lactulose and mannitol as probes for intestinal permeability assessment with untargeted screening of small molecules. Urine samples were collected from patients major depression healthy controls part clinical study at psychiatric department. Using injection/dual chromatography setup, quantified by hydrophilic interaction liquid (HILIC) in targeted assay, while drugs their metabolites profiled an manner reversed-phase separation. Rigorous method development validation allowed selective separation isomers consequently accurate quantification urine. Internal standardization compound specific stable isotope-labeled standards enabled excellent analytical figures merit such high recoveries, precision (< 5%), working range (5 orders magnitude). Within one run, was assessed together metabolites, allowing to screen confounding patient compliance therapeutic scheme.