title: Abiotic amidine and guanidine hydrolysis of lamotrigine-N2-glucuronide and related compounds in wastewater: The role of pH and N2-substitution on reaction kinetics.
abstract: The stability of lamotrigine (LMG) and its principal human metabolite, lamotrigine N2-glucuronide (LMG-N2-G), was studied as a function of pH (4-9). While LMG was stable across the entire pH range, under neutral-basic conditions, LMG-N2-G was converted to three transformation products (TPs) which were identified using high resolution mass spectrometry (HRMS). The MS fragmentation studies indicated that two TPs were the result of the hydrolysis of the amidine and guanidine moieties. The third TP detected was an intermediate in the guanidine hydrolysis reaction. In order to evaluate the transformation kinetics of the LMG-N2-G degradation, another set of pH-dependent experiments was carried out in hospital effluent, wastewater influent and effluent spiked at 20 and 200 nM after pH adjustment (pH 6.5, 7, 8, 8.5 and 9), demonstrating that, at higher pH, LMG-N2-G is degraded at higher rate. Later, the pH-dependent stability of related compounds with different nitrogen N2-substituents (N2-R) on the 1,2,4-triazine ring was studied. This revealed that because of different imino tautomer equilibrium LMG (N2-H) and LMG-N2-oxide ((+)N2-O(-)) were stable at all pHs but N2-methyl-LMG (N2-CH3) as well as LMG-N2-G were susceptible to amidine and guanidine hydrolysis at basic pH. Finally, hospital effluent samples collected over the course of one week were monitored for their presence. LMG, LMG-N2-G and two of its TPs were detected with concentrations ranging between 0.01 and 1 μgL(-1).
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: University of Barcelona (UB), Faculty of Pharmacy, Department of Pharmacology and Medicinal Chemistry, Avga. Joan XXIII s/n, E-08028 Barcelona, Spain; Department of Biomedicinal Chemistry, Research Unit on BioActive Molecules (RUBAM), IQAC-CSIC, c/Jordi Girona, 18-26, 08034 Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Delgado
authors.affiliation: Department of Biomedicinal Chemistry, Research Unit on BioActive Molecules (RUBAM), IQAC-CSIC, c/Jordi Girona, 18-26, 08034 Barcelona, Spain.
authors.forename: J Luis
authors.initials: JL
authors.lastname: Abad
authors.affiliation: Water and Soil Quality Research Group, Department of Environmental Chemistry, IDAEA-CSIC, c/Jordi Girona, 18-26, 08034 Barcelona, Spain. Electronic address: spsqam@cid.csic.es.
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, c/Emili Grahit, 101, Edifici H(2)O, Parc Científic i Tecnològic de la Universitat de Girona, E-17003 Girona, Spain.
authors.forename: Damià
authors.initials: D
authors.lastname: Barceló
mesh_terms: D000578:Amidines; D019791:Guanidine; D006146:Guanidines; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D062065:Wastewater / Q000737:chemistry*
chemical_list: D000578:Amidines; D019791:Guanidine; D006146:Guanidines; D062065:Wastewater
keywords: Amidine and guanidine hydrolysis transformation products; Imino tautomers; LC-HRMS; Lamotrigine-N2-glucuronide; Wastewater; pH stability