Human Metabolite Lamotrigine-N²-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.

A systematic model identification method for chemical transformation pathways – the case of heroin biomarkers in wastewater

“…3 correspond to significant skewedness of the histograms. Nevertheless, the two additional pathways found in this study are in agreement with existing literature, in which incomplete deconjugation of glucuronide metabolites to the respective parent substance was shown in wastewater for morphine 53 , lamotrigine 54 and sulfamethoxazole 55 .…”

Performance of secondary wastewater treatment methods for the removal of contaminants of emerging concern implicated in crop uptake and antibiotic resistance spread: A review

“…This behaviour may be due to its hydrophilic nature (logKow <3) and chemical stability (Nakada et al, 2006). Similar behaviour is observed for lamotrigine which, in two recent studies (Bollmann et al, 2016;Zonja et al, 2016), showed a consistent concentration increase in the effluent.…”

“…Metformin BDL->10000 (Margot et al, 2013;Kosma et al, 2015) Carbamazepine 54-185054- (Clara et al, 2005bNakada et al, 2006;Margot et al, 2013) Lamotrigine 13-1110 (Bollmann et al, 2016;Zonja et al, 2016) Triclosan 500-6100 (Lindstrom et al, 2002;Singer et al, 2002;Halden and Paull 2005;Ying and Kookana 2007) Industrial Chemicals…”

“…From the data analysis of CAS, we can conclude that CEC removal efficiency is strongly affected by HRT and SRT. To give a general idea of the limit values, according to Metcalfe et al, (2003), worst performance is observed in plants having HRT ≤ 7 hr and SRT ≤ 1.9 d. (Gobel et al, 2005) Erythromycin (-14)-100 (Yang and Carlson 2004;Gobel et al, 2005;Gros et al, 2006) Clarithromycin 37 (Margot et al, 2013) Azithromycin 11-44 (Gobel et al, 2005;Loganathan et al, 2009;Margot et al, 2013) Sulfamethoxazole 35-84 (Gobel et al, 2005;Margot et al, 2013;Zhou et al, 2013) Enrofloxacin ~ 0 (Watkinson et al, 2007) Ciprofloxacin 63-90 (Margot et al, 2013;Zhou et al, 2013) Other pharmaceuticals/antimicrobials Diclofenac <0-81 (Clara et al, 2005b;Margot et al, 2013;Luo et al, 2014;Sari et al, 2014) Metformin 78-99 (Kosma et al, 2015) Carbamazepine (-90)-(-3) (Metcalfe et al, 2003;Clara et al, 2005b;Nakada et al, 2006;Margot et al, 2013) Lamotrigine (-361)-(-38) (Bollmann et al, 2016;Zonja et al, 2016) Triclosan 34-99 (Lindstrom et al, 2002;Singer et al, 2002 (Zhang et al, 2013;Zhang et al, 2015a) Perfluoropentanoic acid (PFPeA) (-400)-50 (Pan et al, 2011;Kim et al, 2012;Zhang et al, 2013;Zhang et al, 2015a) Perfluorohexanoic acid (PFHxA) (-226)-39 (Kim et al, 2012;Zhang et al, 2013;…”

Fate of carbamazepine, its metabolites, and lamotrigine in soils irrigated with reclaimed wastewater: Sorption, leaching and plant uptake

“…Lamotrigine is a relatively new drug that was recently detected for the first time in wastewater, surface water and drinking water (Ferrer and Thurman, 2010). In environmental samples, lamotrigine (at concentrations of up to 1 mg L À1 ) was accompanied with its primary metabolite, lamotrigine-2-N-glucuronide (Ferrer and Thurman, 2012;Writer et al, 2013b;Zonja et al, 2015). This metabolite, though pharmacologically inactive, can undergo deconjugation in water to form the parent compound (Ferrer and Thurman, 2010).…”