Secondary Effects of Hypochlorite Treatment on the Emerging Pollutant Candesartan: The Formation of Degradation Byproducts and Their Toxicological Profiles

In recent years, many studies have reported the frequent detection of antihypertensive agents such as sartans (olmesartan, valsartan, irbesartan and candesartan) in the influents and effluents of wastewater treatment plants (WWTPs) and in the superficial waters of rivers and lakes in both Europe and North America. In this paper, the degradation pathway for candesartan (CAN) was investigated by simulating the chlorination process that is normally used to reduce microbial contamination in a WWTP. Twelve isolated degradation byproducts (DPs), four of which were isolated for the first time, were separated on a C-18 column by employing a gradient HPLC method, and their structures were identified by combining nuclear magnetic resonance and mass spectrometry and comparing the results with commercial standards. On the basis of these results, a mechanism of formation starting from the parent drug is proposed. The ecotoxicity of CAN and its DPs was studied by conducting a battery of ecotoxicity tests; bioassays were performed using Aliivibrio fischeri (bacterium), Daphnia magna (planktonic crustacean) and Raphidocelis subcapitata (alga). The ecotoxicity results shed new light on the increased toxicity of DPs compared with the parent compound.

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Amoxicillin in Water: Insights into Relative Reactivity, Byproduct Formation, and Toxicological Interactions during Chlorination

Applied Sciences ◽

10.3390/app11031076 ◽

2021 ◽

Vol 11 (3) ◽

pp. 1076

Author(s):

Antonietta Siciliano ◽

Marco Guida ◽

Giovanni Libralato ◽

Lorenzo Saviano ◽

Giovanni Luongo ◽

...

Keyword(s):

Antibacterial Activity ◽

Wastewater Treatment ◽

Wastewater Treatment Plants ◽

Parent Compound ◽

Treatment Plant ◽

Parent Drug ◽

Degradation Pathway ◽

Hplc Method ◽

Consistent Finding ◽

Byproduct Formation

In recent years, many studies have highlighted the consistent finding of amoxicillin in waters destined for wastewater treatment plants, in addition to superficial waters of rivers and lakes in both Europe and North America. In this paper, the amoxicillin degradation pathway was investigated by simulating the chlorination process normally used in a wastewater treatment plant to reduce similar emerging pollutants at three different pH values. The structures of 16 isolated degradation byproducts (DPs), one of which was isolated for the first time, were separated on a C-18 column via a gradient HPLC method. Combining mass spectrometry and nuclear magnetic resonance, we then compared commercial standards and justified a proposed formation mechanism beginning from the parent drug. Microbial growth inhibition bioassays with Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus were performed to determine the potential loss of antibacterial activity in isolated degradation byproducts. An increase of antibacterial activity in the DPs was observed compared to the parent compound.

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LC and NMR Studies for Identification and Characterization of Degradation Byproducts of Olmesartan Acid, Elucidation of Their Degradation Pathway and Ecotoxicity Assessment

Molecules ◽

10.3390/molecules26061769 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1769

Author(s):

Giovanni Luongo ◽

Antonietta Siciliano ◽

Giovanni Libralato ◽

Sara Serafini ◽

Lorenzo Saviano ◽

...

Keyword(s):

Antihypertensive Drugs ◽

Treatment Plant ◽

Parent Drug ◽

Degradation Pathway ◽

Nmr Studies ◽

Chlorination Process ◽

Ecotoxicity Tests ◽

Aliivibrio Fischeri ◽

First Time

The discovery of various sartans, which are among the most used antihypertensive drugs in the world, is increasingly frequent not only in wastewater but also in surface water and, in some cases, even in drinking or groundwater. In this paper, the degradation pathway of olmesartan acid, one of the most used sartans, was investigated by simulating the chlorination process normally used in a wastewater treatment plant to reduce similar emerging pollutants. The structures of nine isolated degradation byproducts (DPs), eight of which were isolated for the first time, were separated via chromatography column and HPLC methods, identified by combining nuclear magnetic resonance and mass spectrometry, and justified by a proposed mechanism of formation beginning from the parent drug. Ecotoxicity tests on olmesartan acid and its nine DPs showed that 50% of the investigated byproducts inhibited the target species Aliivibrio fischeri and Raphidocelis subcapitata, causing functional decreases of 18% and 53%, respectively.

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Amoxicillin in Water: Insights Into Relative Reactivity, Byproduct Formation, and Toxicological Interactions During Chlorination

10.20944/preprints202012.0638.v1 ◽

2020 ◽

Author(s):

Antonietta Siciliano ◽

Marco Guida ◽

Giovanni Libralato ◽

Lorenzo Saviano ◽

Giovanni Luongo ◽

...

Keyword(s):

Antibacterial Activity ◽

Wastewater Treatment ◽

Wastewater Treatment Plants ◽

Parent Compound ◽

Treatment Plant ◽

Parent Drug ◽

Degradation Pathway ◽

Hplc Method ◽

Consistent Finding ◽

Byproduct Formation

In recent years, many studies have highlighted the consistent finding of amoxicillin in waters destined for wastewater treatment plants, in addition to superficial waters of rivers and lakes in both Europe and North America. In this paper, the amoxicillin degradation pathway was investigated by simulating the chlorination process normally used in a wastewater treatment plant to reduce similar emerging pollutants at three different pH values. The structures of 16 isolated degradation byproducts (DPs), one of which was isolated for the first time, were separated on a C-18 column via a gradient HPLC method. Then, combining mass spectrometry (MALDI-MS/TOF) and nuclear magnetic resonance, we compared commercial standards and justified a proposed formation mechanism beginning from the parent drug. Microbial growth inhibition bioassays with Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus were performed to determine the potential loss of antibacterial activity in isolated degradation byproducts. An increase of antibacterial activity in the DPs was observed compared to the parent compound.

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The design, synthesis, pharmacokinetic and pharmacodynamic evaluation of acyloxyalkyl-substituted T705 prodrugs

Medicinal Chemistry ◽

10.2174/1573406415666191022143933 ◽

2019 ◽

Vol 15 ◽

Author(s):

Xingzhou Li ◽

Tianhong Zhang ◽

Wu Zhong

Keyword(s):

Plasma Concentration ◽

Development Strategy ◽

Parent Compound ◽

Systemic Exposure ◽

Parent Drug ◽

New Drugs ◽

Structure Modification ◽

Design Synthesis ◽

Pharmacokinetic Properties

Background: The pharmacokinetic properties of T705 are not optimal for the development of new drugs. Objective: To improve the pharmacokinetic properties of T-705, structure modification of T-705 was conducted using a prodrug strategy. Method: The acidic amide H atom (N4-H) of T705 was attempted to be replaced with acyloxyalkyl groups following the prodrugs development strategy for carboxylic acids, and the resulting compounds were investigated whether could work as prodrugs and contribute to improving the pharmacokinetic properties of the parent compound T705 in vivo. Results: 4-acyloxyalkyl-T705 (4a–e), did act as prodrugs in vivo. 4-iso-butyryloxymethyl-T705 (4a) and 4-acetoxymethyl-T705 (4b) could significantly improve the plasma concentration and systemic exposure for T705, compound 4a displayed non inferior anti-influenza activities, compared with its parent drug T705. Conclusion: Our prodrugs development strategy for T705 is feasible, which may serves as a reference to prodrugs development of similar heterocyclic amides compounds.

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Identification, Characterization, and Quantification of Impurities of Safinamide Mesilate: Process-Related Impurities and Degradation Products

Journal of AOAC International ◽

10.5740/jaoacint.16-0218 ◽

2017 ◽

Vol 100 (4) ◽

pp. 1029-1037 ◽

Cited By ~ 1

Author(s):

Liang Zou ◽

Lili Sun ◽

Hui Zhang ◽

Wenkai Hui ◽

Qiaogen Zou ◽

...

Keyword(s):

Degradation Products ◽

Hplc Method ◽

Formation Mechanisms ◽

Stability Indicating ◽

Related Impurities ◽

Related Substances ◽

Water Ph ◽

Bulk Drug ◽

First Time

Abstract The characterization of process-related impurities and degradation products of safinamide mesilate (SAFM) in bulk drug and a stability-indicating HPLC method for the separation and quantification of all the impurities were investigated. Four process-related impurities (Imp-B, Imp-C, Imp-D, and Imp-E) were found in the SAFM bulk drug. Five degradation products (Imp-A, Imp-C, Imp-D, Imp-E, and Imp-F) were observed in SAFM under oxidative conditions. Imp-C, Imp-D, and Imp-E were also degradation products and process-related impurities. Remarkably, one new compound, identified as (S)-2-[4-(3-fluoro-benzyloxy) benzamido] propanamide (i.e., Imp-D), is being reported here as an impurity for the first time. Furthermore, the structures of the aforementioned impurities were characterized and confirmed via IR, NMR, and MS techniques, and the most probable formation mechanisms of all impurities proposed according to the synthesis route. Optimum separation was achieved on an Inertsil ODS-3 column (250 × 4.6 mm, 5 μm), using 0.1% formic acid in water (pH adjusted to 5.0) and acetonitrile as the mobile phase in gradient mode. The proposed method was found to be stability-indicating, precise, linear, accurate, sensitive, and robust for the quantitation of SAFM and its process-related substances, including its degradation products.

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Presence of Mycobacterium avium Subspecies paratuberculosis Monitored Over Varying Temporal and Spatial Scales in River Catchments: Persistent Routes for Human Exposure

Microorganisms ◽

10.3390/microorganisms7050136 ◽

2019 ◽

Vol 7 (5) ◽

pp. 136 ◽

Cited By ~ 4

Author(s):

Hollian Richardson ◽

Glenn Rhodes ◽

Peter Henrys ◽

Luigi Sedda ◽

Andrew J. Weightman ◽

...

Keyword(s):

Mycobacterium Avium ◽

Human Exposure ◽

Infected Animal ◽

Wastewater Treatment Plants ◽

Mycobacterium Avium Subspecies Paratuberculosis ◽

Spatial Scales ◽

Adequate Representation ◽

Temporal And Spatial ◽

First Time ◽

River Catchments

Mycobacterium avium subspecies paratuberculosis (Map) was monitored by quantitative PCR over a range of temporal and spatial scales in the River Tywi catchment. This study shows the persistence of Map over a 10-year period with little change, which correlates with the recognised levels of Johne’s disease in British herds over that period (aim 1). Map was quantified within the river at up to 108 cell equivalents L−1 and was shown to be consistently present when monitored over finer timescales (aim 4). Small wastewater treatment plants where the ingress of human-associated Map might be expected had no significant effect (aim 2). Map was found for the first time to be located in natural river foams providing another route for spread via aerosols (aim 5). This study provides evidence for the environmental continuum of Map from the grazing infected animal via rain driven runoff through field drains and streams into main rivers; with detection at a high frequency throughout the year. Should Map need to be monitored in the future, we recommend that weekly or monthly sampling from a fixed location on a river will capture an adequate representation of the flow dynamics of Map in a catchment (aim 3). The human exposure to Map during this process and its impact on human health remains unquantified.

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Highly Sensitive and Selective Fluorescent Detection of Gossypol Based on BSA-Stabilized Copper Nanoclusters

Molecules ◽

10.3390/molecules24010095 ◽

2018 ◽

Vol 24 (1) ◽

pp. 95 ◽

Cited By ~ 6

Author(s):

Shuangjiao Xu ◽

Kehai Zhou ◽

Dan Fang ◽

Lei Ma

Keyword(s):

High Performance ◽

Signal To Noise Ratio ◽

High Sensitivity ◽

Hplc Method ◽

Fluorescent Detection ◽

Copper Nanoclusters ◽

Highly Sensitive ◽

The Us ◽

Fluorescence Quenching Mechanism ◽

First Time

In this paper, fluorescent copper nanoclusters (NCs) are used as a novel probe for the sensitive detection of gossypol for the first time. Based on a fluorescence quenching mechanism induced by interactions between bovine serum albumin (BSA) and gossypol, fluorescent BSA-Cu NCs were seen to exhibit a high sensitivity to gossypol in the range of 0.1–100 µM. The detection limit for gossypol is 25 nM at a signal-to-noise ratio of three, which is approximately 35 times lower than the acceptable limit (0.9 µM) defined by the US Food and Drug Administration for cottonseed products. Moreover, the proposed method for gossypol displays excellent selectivity over many common interfering species. We also demonstrate the application of the present method to the measurement of several real samples with satisfactory recoveries, and the results agree well with those obtained using the high-performance liquid chromatography (HPLC) method. The method based on Cu NCs offers the followings advantages: simplicity of design, facile preparation of nanomaterials, and low experimental cost.

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Development and Validation of a Reversed-Phase Chiral HPLC Method to Determine the Chiral Purity of Bulk Batches of (S)-Enantiomer in Afoxolaner

Journal of AOAC International ◽

10.5740/jaoacint.16-0096 ◽

2017 ◽

Vol 100 (1) ◽

pp. 65-73

Author(s):

Nilusha Padivitage ◽

Satish Kumar ◽

Abu Rustum

Keyword(s):

Method Development ◽

Specific Rotation ◽

Reversed Phase ◽

Hplc Method ◽

Racemic Mixture ◽

Chiral Hplc ◽

Development Tool ◽

Chiral Purity ◽

Development And Validation ◽

First Time

Abstract Afoxolaner is a new antiparasitic molecule from the isoxazoline family that acts on insect acarine g-aminobutyric acid and glutamate receptors. Afoxolaner is a racemic mixture, which has a chiral center at the isoxazoline ring. A reversed-phase chiral HPLC method has been developed to determine the chiral purity of bulk batches of (S)-enantiomer in afoxolaner for the first time. This method can also be used to verifythat afoxolaner is a racemic mixture, which was demonstrated by specific rotation. ChromSword, an artificial intelligence method development tool, was used for initial method development. The column selected for the final method was CHIRALPAK AD-RH (150 × 4.6 mm, 5 μm particle size), maintained at 45°C, and isocratic elution using water–isopropanol–acetonitrile (40 + 50 + 10, v/v/v) as the mobile phasewith a detection wavelength of 312 nm. The run time for the method was 11 min. The resolution and selectivity factors of the two enantiomers were 2.3 and 1.24, respectively. LOQ and LOD of the method were 1.6 and 0.8 μg/mL, respectively. This method was appropriately validated according to International Conference on Harmonization guidelines for its intended use.

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New Eco-Materials Derived from Waste for Emerging Pollutants Adsorption: The Case of Diclofenac

Materials ◽

10.3390/ma13183964 ◽

2020 ◽

Vol 13 (18) ◽

pp. 3964

Author(s):

Ario Fahimi ◽

Alessandra Zanoletti ◽

Stefania Federici ◽

Ahmad Assi ◽

Fabjola Bilo ◽

...

Keyword(s):

Fly Ash ◽

Wastewater Treatment Plants ◽

Coal Fly Ash ◽

Bottom Ash ◽

Emerging Pollutants ◽

Emerging Pollutant ◽

Pharmaceutical Removal ◽

Heating Treatment ◽

Sustainable Materials ◽

Potential Use

This work proposes new eco-materials for the adsorption of diclofenac (DCF). The large consumption of this nonsteroidal anti-inflammatory drug combined with the inefficiency of wastewater treatment plants (WWTPs) leads to its presence in aquatic environments as an emerging pollutant. The adsorption technique is widely used for pharmaceutical removal. Moreover, due to the large effect of commercial adsorbents, in the frame of the Azure Chemistry approach, new sustainable materials are mandatory for removal as emerging pollutants. The work proposes three adsorbents that were obtained from different stabilization methods of fly ash derived from an incinerator plant; the stabilization techniques involved the use of various industrial by-products such as bottom ash, flue gas desulphurization residues, coal fly ash, and silica fume. The best performance, although less than activated carbon, was obtained by COSMOS (COlloidal Silica Medium to Obtain Safe inert: the case of incinerator fly ash), with a removal efficacy of approximately 76% with 15 g/L of material. Several advantages are expected not only from the DCF removal but also from an economic perspective (the newly obtained adsorbents are eco-materials, so they are cheaper in comparison to conventional adsorbents) and in terms of sustainability (no toxic reagents and no heating treatment are involved). This work highlights the adsorption performance of the new eco-materials and their potential use in WWTPs.

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Biological Removal and Fate Assessment of Diclofenac Using Bacillus subtilis and Brevibacillus laterosporus Strains and Ecotoxicological Effects of Diclofenac and 4′-Hydroxy-diclofenac

Journal of Chemistry ◽

10.1155/2020/9789420 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

Camille Grandclément ◽

Anne Piram ◽

Marie-Eléonore Petit ◽

Isabelle Seyssiecq ◽

Isabelle Laffont-Schwob ◽

...

Keyword(s):

Vibrio Fischeri ◽

High Resolution Mass Spectrometry ◽

Parent Compound ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Bacterial Consortia ◽

Brevibacillus Laterosporus ◽

Emerging Pollutant ◽

Significant Difference ◽

Rrna Gene Sequencing

Since bacterial consortia involved in conventional wastewater treatment processes are not efficient in removing diclofenac (DCF), an emerging pollutant frequently detected in water bodies, the identification of microorganisms able to metabolise this pharmaceutical compound is relevant. Thus, DCF removal was investigated using bacteria isolated from aqueous stock solutions of this micropollutant and identified as Bacillus and Brevibacillus species using 16S rRNA gene sequencing. A 100% DCF removal was achieved after 17 hours of experiment at 20°C in a nutrient medium; the biodegradation kinetic followed a pseudo-first order (kbiol = 11 L·gSS−1·d−1). Quantitative assessment of DCF removal showed that its main route was biotic degradation. The main degradation product of DCF, 4′-hydroxy-diclofenac (4′-OH-DCF), was identified using liquid chromatography-electrospray ionisation high-resolution mass spectrometry. Since the ecotoxicological impact of 4′-hydroxy-diclofenac was not reported in the literature, the ecotoxicity of DCF and its metabolite were tentatively evaluated using Vibrio fischeri bioassays. Results from these tests showed that this metabolite is not more toxic than its parent compound and may hopefully be an intermediate product in the DCF transformation. Indeed, no significant difference in ecotoxicity was observed after 30 min between DCF (50 should be writtten in subscript all along the manuscript in EC50 = 23 ± 4 mg·L−1) and 4′-hydroxy-diclofenac (EC50 = 19 ± 2 mg·L−1). Besides, the study highlighted a limit of the Microtox® bioassay, which is largely used to assess ecotoxicity. The bioluminescence of Vibrio fischeri was impacted due to the production of microbial activity and the occurrence of some carbon source in the studied medium.

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