title: Further exploring the absorption and enterocyte metabolism of quercetin forms in the Caco-2 model using nano-LC-TOF-MS.
abstract: When using the Caco-2 intestinal model, the low uptake, intracellular presence at low levels as well as generation of trace metabolites may limit the analysis of flavonoids. To overcome these limitations, we performed a simple but sensitive methodology based on nano-LC-TOF-MS, using an on-line trapping step. The analytical method was validated for quercetin, quercetin 3-O-glucoside, and quercetin 3-O-glucuronide and the reliability for characterization using lock-mass calibration was also assessed along the linear range. Afterwards, the in vitro absorption, metabolism, and cellular occurrence were explored with the proposed methodology. The apparent permeability coefficient in the absorptive direction and the cellular accumulation were higher for quercetin aglycone, with a value of 2.61 × 10(-6) cm/s and relative amounts of 0.73 and 1.17% in the cytosolic and solid particle fraction at the end of the assay, respectively. Alternatively, the net efflux ratio was lower for quercetin than for their derivatives. Moreover, depending on the structure of the parent compound, metabolites were generated by glucuronidation, sulfation, and methylation.
authors.affiliation: Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Granada, Spain.|Research and Development Functional Food Centre (CIDAF), Bioregión Building, Health Science Technological Park, Granada, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Del Mar Contreras
authors.affiliation: Research and Development Functional Food Centre (CIDAF), Bioregión Building, Health Science Technological Park, Granada, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Borrás-Linares
authors.affiliation: Instituto de Biología Molecular y Celular (IBMC), Miguel Hernández University, Elche, Alicante, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Herranz-López
authors.affiliation: Instituto de Biología Molecular y Celular (IBMC), Miguel Hernández University, Elche, Alicante, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Micol
authors.affiliation: Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Granada, Spain.|Research and Development Functional Food Centre (CIDAF), Bioregión Building, Health Science Technological Park, Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Segura-Carretero
mesh_terms: D018938:Caco-2 Cells; D002853:Chromatography, Liquid / Q000379:methods*; D020895:Enterocytes / Q000378:metabolism*; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D013058:Mass Spectrometry / Q000379:methods*; D008954:Models, Biological; D036103:Nanotechnology / Q000379:methods; D011794:Quercetin / Q000032:analysis* / Q000493:pharmacokinetics*; D015203:Reproducibility of Results
chemical_list: D011794:Quercetin
keywords: Absorption; Caco-2 model; Flavonoids; Miniaturized technique; Nano-LC