title: Human Metabolite Lamotrigine-N(2)-glucuronide Is the Principal Source of Lamotrigine-Derived Compounds in Wastewater Treatment Plants and Surface Water.
abstract: Wastewater and surface water samples, extracted with four solid-phase extraction cartridges of different chemistries, were suspect-screened for the anticonvulsant lamotrigine (LMG), its metabolites, and related compounds. LMG, three human metabolites, and a LMG synthetic impurity (OXO-LMG) were detected. Preliminary results showed significantly higher concentrations of OXO-LMG in wastewater effluent, suggesting its formation in the wastewater treatment plants (WWTPs). However, biodegradation experiments with activated sludge demonstrated that LMG is resistant to degradation and that its human metabolite lamotrigine-N(2)-glucuronide (LMG-N2-G) is the actual source of OXO-LMG in WWTPs. In batch reactors, LMG-N2-G was transformed, following pseudo-first-order kinetics to OXO-LMG and LMG, but kinetic experiments suggested an incomplete mass balance. A fragment ion search applied to batch-reactor and environmental samples revealed another transformation product (TP), formed by LMG-N2-G oxidation, which was identified by high-resolution mass spectrometry. Accounting for all TPs detected, a total mass balance at two concentration levels in batch reactors was closed at 86% and 102%, respectively. In three WWTPs, the total mass balance of LMG-N2-G ranged from 71 to 102%. Finally, LMG-N2-G and its TPs were detected in surface water samples with median concentration ranges of 23-139 ng L(-1). The results of this study suggest that glucuronides of pharmaceuticals might also be sources of yet undiscovered, but environmentally relevant, transformation products.
authors.affiliation: Water and Soil Quality Research Group, Department of Environmental Chemistry, IDAEA-CSIC , c/Jordi Girona, 18-26, 08034 Barcelona, Spain.
authors.forename: Bozo
authors.initials: B
authors.lastname: Zonja
authors.affiliation: Water and Soil Quality Research Group, Department of Environmental Chemistry, IDAEA-CSIC , c/Jordi Girona, 18-26, 08034 Barcelona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pérez
authors.affiliation: Water and Soil Quality Research Group, Department of Environmental Chemistry, IDAEA-CSIC , c/Jordi Girona, 18-26, 08034 Barcelona, Spain.|Catalan Institute of Water Research, Edifici H2O, Parc Científic i Tecnològic de la Universitat de Girona , c/Emili Grahit, 101, E-17003 Girona, Spain.
authors.forename: Damià
authors.initials: D
authors.lastname: Barceló
mesh_terms: D006801:Humans; D000077213:Lamotrigine; D014227:Triazines / Q000032:analysis* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D062065:Wastewater / Q000737:chemistry*; D014874:Water Pollutants, Chemical / Q000032:analysis*; D018508:Water Purification
chemical_list: D000077213:Lamotrigine; D014227:Triazines; D062065:Wastewater; D014874:Water Pollutants, Chemical; C074259:lamotrigine 2-N-glucuronide