Free chlorine reactions of angiotensin II receptor antagonists: Kinetics study, transformation products elucidation and in-silico ecotoxicity assessment

Abstract

Angiotensin II receptor antagonists (ARA II) are widely employed in the treatment of hypertension-related diseases. Because of their partial metabolization and limited biodegradability, these drugs have become ubiquitous pollutants in the aquatic environment, including surface water. This research evaluated the reactivity of the ARA II drugs: irbesartan (IRB), losartan (LOS) telmisartan (TEL) and valsartan (VAL) with free chlorine. Responses of parent compounds and their transformation products (TPs) were followed by liquid chromatography (LC) with quadrupole (Q) time-of-flight (TOF) mass spectrometry. Degradation experiments were carried out using ultrapure and river water samples, adjusted at different pHs and, in some cases, adding a small amount (ng mL level) of bromide salts. Whilst TEL and VAL remained stable in presence of relatively high concentrations of free chlorine (10 mg L), IRB and LOS were removed according to a pseudo-first order kinetics model. Considering an initial chlorine concentration of 10 mg L, their half-lives varied between 6 and 734 min, depending mostly on the water pH. IRB reacted with free chlorine through hydroxylation processes, with and without molecular cleavage and re-arrangements in the imidazolone ring. Its TPs showed a lower in-silico predicted toxicity than the parent drug. In case of LOS, two major competitive degradation routes were identified. They involved replacement of the methanol group attached to the imidazole cycle by chlorine or bromine, and the cleavage of this cycle with removal of the chlorinated carbon and the nitrogen in alpha position. The TPs generated following the first route are predicted to be more toxic than LOS.

Selective determination of sartan drugs in environmental water samples by mixed-mode solid-phase extraction and liquid chromatography tandem mass spectrometry

“…Moreover, the spectrum of IRB-OH depicted in Fig. S4 matched that previously published for a derivative observed during reaction of IRB with free chlorine and assigned to IRB hydroxylated in the terminal carbon of the alkyl chain attached to the imidazole ring (Carpinteiro et al, 2019). The presence of a hydroxylated form of IRB in treated wastewater and surface water samples was also described by Letzel and co-workers (Letzel et al, 2015).…”

“…Some sartans are stable during oxidative water treatments (photolysis, free chlorine and ozone addition), either tested at laboratory scale (Blum et al, 2017), or applied in tap water production plants (Huerta-Fontela et al, 2011). In other cases, such as losartan (LOS), transformation products arising from chemical oxidative treatments are deemed to be more toxic than the precursor drug (Carpinteiro et al, 2019). In addition to their stability during oxidative treatments, olmesartan (OLM) and candesartan (CAN) are not removed during soil infiltration of treated wastewaters (Hellauer et al, 2018), which is usually employed to recharge groundwater aquifers.…”

Ecotoxicity and genotoxicity assessment of losartan after UV/H2O2 and UVC/photolysis treatments

“…The authors suggest two possible pathways for the LOS degradation: the reaction between hydroxyl radical and the alcohol moiety of LOS or the addition of HO ● to the carbon double bond, forming several isomers of biphenyl hydroxylation. Then, chlorine is removed and followed by hydroxylation of carbon at 2 and 5 position, and consequently the opening of the imidazole ring (Carpinteiro et al 2019 ). Considering that LOS contain chlorine atoms in its structure, the Cl ∙ radicals may be generated, which would contribute to the degradation of the molecule under UVC-irradiation (Starling et al 2019 ).…”

“…The ● OH radicals from the UV/H 2 O 2 treatment can react with organic compounds containing π-bonds, as unsaturated hydrocarbons and aromatic rings, by hydroxylation reaction (Melo et al 2009 ) and generate toxic by-products to D. magna . Carpinteiro et al ( 2019 ) verified that the LOS degradation by free chlorine treatment can also form toxic by-products to D. magna via electrophilic halogenation and hydroxylation reactions. According to the authors, the CE 50/48h in silico of by-products, using the ECOSAR software , was at ranged from 8 to 0.008 mg L −1 .…”

Presence and Reduction of Anthropogenic Substances with UV Light and Oxidizing Disinfectants in Wastewater—A Case Study at Kuopio, Finland

“…Losartan can undergo structural modification resulting in formation of valsartan acid, which is a persistent pollutant ending up into activated sludge [53]. Losartan can also be found in various water matrices such as surface water and rivers [54]. It has been shown to be present in municipal wastewaters, e.g., in Colombia losartan has been detected in wastewater effluent at concentrations of 1.97 and 1.00 µg L −1 [55].…”