N-nitrosodimethylamine Formation Research Articles

Ranitidine: A Proposed Mechanistic Rationale for NDMA Formation and a Potential Control Strategy

The formation of N-nitrosodimethylamine (NDMA) in ranitidine hydrochloride drug substance (DS) and drug products has attracted considerable attention over the last few years. The drug structure is unusual in that it contains a vinyl nitro moiety. Although a variety of studies have been carried out to understand how NDMA is formed in the DS solids, a mechanistic description of NDMA formation has remained elusive. A new mechanistic view of NDMA formation is detailed here. Autoxidation of ranitidine can rationalize nitrite ion and dimethylamine liberation from ranitidine. The subsequent nitrosation is argued to be due to conversion of nitrite ion to the gas phase nitrosating agent nitrosyl chloride, NOCl. Oxygen scavenging packaging systems should be able to stop the autoxidation, and thus shut down the nitrite release from ranitidine. Without nitrite release NDMA cannot form. This may provide a practical means to stabilize ranitidine DS and solid dosage formulations against NDMA formation.

Identification of transformation products during Doxylamine chloramination for NDMA mitigation

ABSTRACT N-nitrosodimethylamine (NDMA) is a disinfection byproduct that forms at the presence of an organic nitrogen precursor. Doxylamine, an antihistaminic pharmaceutical, is a precursor of NDMA and has been shown to form NDMA in the presence of chloramine. In this study, the effect of Doxylamine as an NDMA precursor has been further studied during chloramination. The end product and byproducts during chloramination were investigated using a high-resolution mass spectrometer by taking samples at different time intervals. Results suggest that NDMA is not the only end product forming during chloramination of Doxylamine and several transformation products that do not end up as NDMA may form. A group of these transformation products have been selected based on their relative amounts during chloramination with time and notated as Focus Tentative Transformation Products (FTTPn). The identification of these byproducts will make it easier to study the conditions during chloramination that may favour these ‘known’ transformation products with the use of less sophisticated analytical instruments. Then, it might lead to the establishment of chloramination protocols that will minimise the formation of NDMA from its precursors.

N-Nitrosodimethylamine formation in metformin hydrochloride sustained-release tablets: Effects of metformin and hypromellose used in drug product formulation

In recent years, nitrosamines have been discovered in some types of drug products that becomes a current regulatory hotspot, and have attracted a lot attention from both regulatory authorities and industry. This manuscript provided an industry perspective on the nitrosamines research. A liquid chromatography coupled with tandem mass spectrometry（LC-MS/MS）method was developed and applied for the quantification of N-nitrosodimethylamine (NDMA) in metformin hydrochloride sustained-release tablets (MET). The key factors resulting in the NDMA formation in MET were identified through forced degradation and drug-excipient studies, which included high temperature, dimethylamine, strong alkali and oxidation conditions, peroxide and alkaline components contained in the formulation as well as the nitrite and nitrate impurities that might be presented in certain excipients. Further, API particle size and water content of the drug product would also affect the growth rate of NDMA. Therefore, the following mitigation strategies to reduce the risk of nitrosamines in the finished drug product are proposed in this manuscript: 1) avoid the use of excipients containing nitrite, nitrate and peroxide impurities; 2) avoid high temperature and strong alkaline environment in the production and storage condition; 3) maintain an appropriate water content level in the formulation. Based on the above principles, it was recommended to add antioxidant or incorporate excipient such as Na2CO3 to modify the formulation pH to weak basic environment in the formulation of MET, which can could effectively prevent formation of NDMA in the stability process.

N-Nitrosation in the absence of nitrosating agents in pharmaceuticals?

The possibility of N-Nitrosation in the absence of nitrosating agents was studied on model solutions and film coated tablets containing metformin. N-nitrosodimethylamine (NDMA) and N-nitrosation precursors (dimethylamine and nitrites) were determined using previously published fully validated analytical methods. Alternative routes to N-nitrosation were found. Dimethylamine can undergo an oxidation to nitrite in the presence of strong oxidants (e.g., H2O2), as was observed during wastewater treatment in several published works. The resulting nitrite can consecutively act as a nitrosating agent. We proved that the described reaction indeed leads to N-nitrosation (NDMA formation in case of dimethylamine precursor) in model solutions made of dimethylamine and H2O2. An experiment was designed in order to prove those reactions take place in dosage forms. Film coated tablets present a highly heterogenous system with several solid phases and low water activity, which is in stark contrast to the liquid wastewater, where this reaction was originally studied. Despite that, the described reaction took place even in the tablets, but only to a small degree. The amount formed via this alternative route corresponds to less than 10 % of the total formed NDMA. The pH optimum of this alternative route lies in the alkaline range which was confirmed by the determined NDMA concentration in model solutions. The solid phase system (i.e., tablets) was found to behave differently. The addition of Na2CO3 into the tablets during manufacture resulted in tablets without NDMA (cNDMA < LOQ) even in batches spiked with both dimethylamine and H2O2. Thus, adjusting the pH of the solid dosage forms remains a sufficient measure of controlling N-nitrosamines in the product, even in product with limit amounts of oxidating agent (H2O2) and N-nitrosation precursor (dimethylamine).

Comparison of the formation of N-nitrosodimethylamine (NDMA) from algae organic matter by chlor(am)ination and UV irradiation

Microcystis aeruginosa (M. aeruginosa, blue-green algae) blooms frequently in drinking water reservoirs and subsequently causes the formation of disinfection by-products (DBPs) after disinfection, which may pose a potential health risk. In this study, the formation of N-nitrosodimethylamine (NDMA) was evaluated from algal organic matter (AOM) including extracellular organic matter (EOM) and intracellular organic matter (IOM) during the disinfection process of chlorination, chloramination, or ultraviolet (UV) irradiation. The effects of a variety of factors, including reaction times, disinfectant dosages and pH, on the NDMA formation by three different disinfection methods were investigated. Additionally, this study evaluated the nitrogen sources involved in NDMA formation during chloramination of EOM and IOM using 15N-labeled monochloramine. The results showed that the NDMA formation by three different disinfection methods were ranked in the order of chlorination > UV irradiation ≈ chloramination and the specific yield from EOM was greater than that from IOM regardless of disinfection method. The yields of NDMA firstly increased and then plateaued as time prolonged during the chlorination and chloramination of AOM. Similarly, the NDMA formation from EOM was firstly increased and then remained constant with the increase of the disinfectant dosage, while it was gradually increased for IOM. The solution pH highly influenced the NDMA formation during chlorination and chloramination, while exhibited a little impact under UV irradiation. Moreover, fluorescence excitation-emission (EEM) analysis confirmed that soluble microbial by-product-like (SMPs) in EOM and IOM were the major precursors in algal-derived organic matter that contributed to the NDMA formation. Chloramination of EOM and IOM using isotope 15N-labeled monochloramine indicated that the nitroso group of the formed NDMA originates mainly from EOM and IOM of algal cells.

Effect of activated sludge treatment on the formation of N[sbnd]nitrosamines under different chloramination conditions

Municipal wastewater discharge is considered as one of the main sources of N-nitrosamine precursors which can impact the qualities of downstream source waters and reclaimed wastewaters for potable reuse. NNitrosamine precursors can be removed to various degrees during biological wastewater treatment (e.g., the activated sludge (AS) process). So far, little is known about the impact of the AS process on N-nitrosamine formation under practical disinfection condition (e.g., uniform formation condition (UFC)). In this study, N-nitrosamine UFC from selected model compounds, sewage components (i.e., blackwaters and greywaters) and sewage samples were comprehensively investigated during batch AS treatment tests. NNitrosodimethylamine (NDMA) formation from the tested precursor compounds (i.e., trimethylamine (TMA) and sumatriptan (SMTR)) under UFC chloramination decreased mostly after 6 or 24 hr treatment with different types of AS (i.e., domestic rural AS, domestic urban AS, and textile AS), and the reductions in NDMA UFC were comparable to their NDMA formation potential (FP) reductions. In urine and feces blackwaters, NDMA UFC increased after 6 or 24 hr treatment with the domestic (i.e., rural and urban) AS, while NDMA FP decreased substantially. The increases in NDMA UFC after AS treatment was presumably attributed to the removal of bulk organic matters (e.g., dissolved organic carbon (DOC)) which favored NDMA formation under UFC. On the other hand, in laundry greywaters having relatively abundant DOC, N-nitrosamine UFC was less affected by DOC removal before or after AS treatment, but decreased to similar degrees with N-nitrosamine FP. In sewage samples collected from wastewater treatment plants, N-nitrosamines UFC tended to increase or remain constant during AS treatment, despite the decreases in their FPs. These results suggest that biological wastewater treatment (e.g., the AS process) may not effectively reduce N-nitrosamine formation (e.g., measured under UFC) partially because the concurrent removal of bulk organic matters (e.g., DOC) favored N-nitrosamine formation in s econdary effluents.

Avoiding N-nitrosodimethylamine formation in metformin pharmaceuticals by limiting dimethylamine and nitrite

Since late 2019, concerns regarding trace levels of the probable human carcinogen N-dimethylnitrosamine (NDMA) in Metformin-containing pharmaceuticals have been an issue if they exceeded the maximum allowable intake of 96 ng/day for a medicine with long-term intake. Here, we report results from an extensive analysis of NDMA content along the active pharmaceutical ingredient (API) manufacturing process as well as two different drug product manufacturing processes. Our findings confirm that Metformin API is not a significant source of NDMA found in Metformin pharmaceuticals and that NDMA is created at those steps of the drug product manufacturing that introduce heat and nitrite. We demonstrate that reduction of nitrite from excipients is an effective means to reduce NDMA in the drug product. Limiting residual dimethylamine in the API has proven to be another important factor for NDMA control as dimethylamine leads to formation of NDMA in the drug products. Furthermore, analysis of historical batches of drug products has shown that NDMA may increase during storage, but the levels reached were not shelf-life limiting for the products under study.

High concentrations of dissolved organic nitrogen and N-nitrosodimethylamine precursors in effluent from biological nutrient removal process with low dissolved oxygen conditions

The presence of dissolved organic nitrogen (DON) in biological nutrient removal (BNR) effluent has led to increased concern about its adverse effects on wastewater discharge and reuse applications. Previous studies have demonstrated efficient biological inorganic nitrogen removal in BNR under low dissolved oxygen (DO) conditions; however, information on DON is scarce. This study investigated low-DO effects on DON and N-nitrosodimethylamine (NDMA) precursor concentrations in BNR effluents. Identical BNR reactors consisting of an external real-time DO intelligent control system were operated at three different DO concentrations (0.3, 1.0, and 4.0 mgO2/L). Surprisingly, significantly higher values of effluent DON (p<0.05, t-test) and NDMA precursors (p<0.01, t-test) were observed at lower DO levels. Ultrahigh-resolution mass spectrometry analysis showed that molecules produced by microbes at low-DO levels exhibited high proteins/amino sugars-like and low normal oxidation state of carbon characteristics, which possibly acted critical roles in NDMA formation. Furthermore, path analysis by partial least-squares path modeling suggested that NDMA formation potential had strong associations with microbe-DON network stability of microbe-DON co-occurrence interactions (r=0.979, p<0.01). These results highlight the necessity of reconsidering the feasibility of BNR systems operating at low-DO concentrations considering the adverse effects of DON on wastewater discharge and reuse applications.

Nitrite-enhanced N-nitrosamines formation during the simulated tetracycline polluted groundwater chlorination: Experimental and theoretical investigation

N-nitrosamines (NAs), a class of emerging nitrogenous disinfection byproducts, have been detected remarkably in drinking/reclaimed water. There is a significant risk of excessive levels of NAs in the chlorination of the polluted source water, especially in the direct chlorination of nitrite-enriched groundwater. Considering the co-pollution of nitrite and micro-organic pollutants on groundwater, experiments were conducted on chlorination of nitrite-enriched water with precursor of antibiotics, and it was confirmed that the Cl 2 : N (molar ratio of chlorine to nitrite), contacting time, pH, and DO appreciably influenced the NAs formation potential. The molecular electric potential revealed that different dissociation status of precursors has a specific correlation with NAs formation potential (FP). The nitrite significantly increased the NAs FP because the reactive nitrogen species (RNS) formed in the oxidation process from nitrite to nitrate. Sequences of transformation products are determined to support the RNS promoted hypothesis of N-nitrosodimethylamine (NDMA) formation mechanism; furthermore, theoretical investigation in the reaction of dimethylamine (DMA) with different RNS verified the above hypothesis. • NDMA FP significantly promoted in chlorination of nitrite-enriched groundwater. • DO is not a key factor to NDMA formation in nitrite-enriched situation. • RNS enhanced-nitrosation pathway was proposed. • NDEA has been detected along with NDMA formation.

NDMA formation during ozonation of DMAPA: Influencing factors, mechanisms, and new pathway exploration

Aliphatic amines, common constituents that contribute to dissolved organic nitrogen (DON), can quickly react with ozone due to the lone electron pair on the nitrogen atom and this may produce carcinogen N-Nitrosodimethylamine (NDMA). 3-(Dimethylamino)-1-propylamine (DMAPA) was chosen as a representative to elucidate the NDMA formation characteristics, kinetic rates, reaction pathways, and influencing factors during ozonation in this study. The results demonstrated that NDMA generated directly from DMAPA during ozonation. Moreover, the NDMA yields increased with ozone dosages. The NDMA molar yield increased and then decreased when the pH raised from 5 to 9, achieving the maximum value at pH 8. Hydroxyl radical (∙OH) played a promotional role in NDMA formation, and its scavenger dramatically cut down its yields. Low levels of Br− facilitated NDMA formation, while the value significantly reduced when Br− was up to 1 mM. The NDMA amount was slightly raised by NO2−, but it was inhibited by NH4+ and NO3−. Moreover, it was also depressed by co-existing components in actual lake water. Based on the result of the Gaussian calculation, the LC-MS/MS and GC–MS analysis, four possible transformation pathways were proposed. The radical recombination was verified to be the primary pathway for ozone promoting NDMA formation from DMAPA.

Effects of ferulic acid on the oxidation stability and nitrozation of myofibrillar proteins under oxidative stress

This study investigated the effects of ferulic acid (FA) on the oxidative stability and nitrozation of porcine myofibrillar proteins (MPs) under oxidative stress. The addition of FA significantly (P < 0.05) inhibited the formation of carbonyl and dityrosine, and reduced the sulfhydryl and free amine content compared with the oxidized MPs. Moreover, FA intensified oxidation-initiated loss of surface hydrophobicity and α-helix conformation, and enhanced protein cross-linking. A progressive quenching of MP endogenous fluorescence intensity was observed with the increase of FA concentration, and the emission wavelength showed a slight red shift. Beside, the addition of FA significantly eliminated sodium nitrite and almost completely inhibited the formation of 3-nitrotyrosine (3-NT) and N-nitrosodimethylamine (NDMA) at 200 μmol/g. Principal component analysis indicated that there were positive correlations between protein oxidation variables (carbonyl, dityrosine and surface hydrophobicity) and nitrozation indexes (3-NT and NDMA), as well as between 3-NT and NDMA. These results suggest that FA could suppress the nitration via controlling MP's oxidation.

Predictable Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry Fragmentation of Ozone-Reactive N-Nitrosodimethylamine Precursors Coupled with In Silico Fragmentation and Ion Mobility-Quadrupole Time-of-Flight Facilitates Their Identification in Sewage

This study investigated the liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) fragmentation of 10 potent model ozone (O3)-reactive N-nitrosodimethylamine (NDMA) precursors bearing (CH3)2N-N or (CH3)2N-(SO2)-N. Fragments (m/z 61.0766, 60.0688 Da loss, and 72.0688 Da loss) were discovered as pertinent diagnostic fragments for precursors bearing (CH3)2N-N, whereas a loss of 108.0119 Da was consistent for precursors bearing (CH3)2N-S(O2)-N. Using the fragments as structural hints on a sewage fraction with a high concentration of O3-reactive precursors, peaks of precursors sharing m/z 61.0766, a 60.0688 Da loss, or both were flagged. Then, using in silico fragmenters and (CH3)2N-N as a substructure filter on online-chemical structure databases, we identified PubChem's compound identifier (PCCID) 141210417 and 1,1,1',1'-tetramethyl-4,4'-(methylene-di-p-phenylene)disemicarbazide (TMDS). TMDS was confirmed using an authentic standard, and ion mobility (IM)-QTOF/MS confirmed its rider peak as PCCID 141210417. PCCID 141210417 is an isomer of TMDS, and its environmental occurrence is associated with technical-grade TMDS and industrial effluents. The estimated contribution of TMDS to the total NDMA formation potential of the sewage fraction was 20-24%, which was suggestive of the significance of PCCID 141210417 and other precursors.

N-nitrosodimethylamine formation during oxidation of N,N-dimethylhydrazine compounds by peroxymonosulfate: Kinetics, reactive species, mechanism and influencing factors

This study found that peroxymonosulfate (PMS) oxidation without activation has the potential to generate a suspected human carcinogen, N-nitrosodimethylamine (NDMA), in water containing N,N-dimethylhydrazine compounds. Considerable amounts of NDMA formed from three compounds by PMS oxidation were observed. 1,1,1′,1′-Tetramethyl-4,4′-(methylene-di-p-phenylene) disemicarbazide (TMDS), which is an industrial antiyellowing agent and light stabilizer, was used as a representative to elucidate the kinetics, transformation products, mechanism and NDMA formation pathways of PMS oxidation. TMDS degradation and NDMA formation involved direct PMS oxidation and singlet oxygen (1O2) oxidation. The oxidation by PMS/1O2 was pH-dependent, which was related to the pH-dependent characteristics of the reactive oxygen species and intermediates. The degradation mechanism of TMDS mainly included the side chain cleavage, dealkylation, and O-addition. NDMA was generated from TMDS mainly via O-addition and 1,1-dimethylhydrazine (UDMH) generation. The cleavage of amide nitrogen in O-addition products and primary amine nitrogen in UDMH are likely the key steps in NDMA generation. The results emphasized that the formation of harmful by-products should be taken into account when assessing the feasibility of PMS oxidation.

Comprehensive Computational Study on Reaction Mechanism of N-Nitroso Dimethyl Amine Formation from Substituted Hydrazine Derivatives During Ozonation

Comprehensive Computational Study on Reaction Mechanism of N-Nitroso Dimethyl Amine Formation from Substituted Hydrazine Derivatives During Ozonation

Bromide strongly influences the formation of reaction products during the ozonation of diclofenac, metoprolol and isoproturon

Bromide as an omnipresent matrix component in wastewater can react with ozone to form hypobromous acid (HOBr). This secondary oxidant can subsequently react with micropollutants but also with formed intermediates. Therefore, bromide and especially HOBr can highly influence the formation of transformation products (TPs). This has already been reported for the ozonation of N,N-dimethylsulfamide leading to the formation of the cancerogenic N-nitrosodimethylamine only in bromide containing waters. In this study, the influence of different bromide and ozone concentrations on the formation of TPs during the ozonation of isoproturon (ISO), metoprolol (METO) and diclofenac (DCF) were investigated. Additionally, TPs were identified, which are formed in the direct reaction of the micropollutants with HOBr with and without subsequent ozonation. The results showed that even if the reactions of ozone with the substances should be favored bromide can highly influence the formation of TPs already at low concentrations. In summary, new TPs after the reaction with HOBr (and subsequent ozonation) could be postulated for ISO, METO and DCF. This underlines that the present water matrix can have a high influence on the formation of TPs and that these mechanisms need to be investigated further.

NDMA analytics in metformin products: Comparison of methods and pitfalls

BackgroundFor nearly three years, the concerns regarding trace levels of N-nitrosamines in pharmaceuticals and the associated cancer risk have significantly expanded and are a major issue facing the global pharmaceutical industry. N-nitrosodimethylamine (NDMA) found in formulations of the popular anti-diabetic drug metformin is a prominent example. This has resulted in product recalls raising the profile within the media. Issues of method robustness, sample preparation and several unexpected sources of nitrosamine contamination have been highlighted as false positive risks. It has become apparent that the identification of the root causes of artefactual formation of nitrosamines must be identified to mitigate risk associated with the analysis. MethodsA comparison study between four laboratories, across three companies was designed, employing orthogonal mass spectrometric methods for the quantification of NDMA in two metformin immediate release (IR) formulations and one extended release (XR) formulation. These were 2x LC-MS/MS, GC–MS/MS and GC-HRMS. ResultsGood agreement of results was obtained for the IR formulations. However, we measured higher concentrations of NDMA in the XR formulation using GC-MS/MS compared to LC-MS/MS. We could show that this was due to artefactual (in situ) formation of NDMA when samples were extracted with dichloromethane. Removal of dimethylamine (DMA) and nitrite from the extracted sample or the addition of a nitrosation scavenger are shown to be effective remedies. NDMA in situ formation was not observed in 10% MeOH or acetonitrile. ConclusionMetformin pharmaceuticals contain traces of the API impurity DMA as well as inorganic nitrite from excipients. This can lead to artefactual formation of NDMA and hence false positive results if DCM is used for sample extraction. Similar artefacts are likely also in other pharmaceuticals if these contain the secondary amine precursor of the respective nitrosamine analyte.

Motivation of reactive oxidation species in peracetic acid by adding nanoscale zero-valent iron to synergic removal of spiramycin under ultraviolet irradiation: Mechanism and N-nitrosodimethylamine formation potential assessment

In this study, nanoscale zero-valent iron (nZVI) was added to motivate the functions of all the reactive oxidation species in peracetic acid (PAA) mixture under ultraviolet (UV) irradiation, and to enhance the removal of spiramycin, which is a typical precursor of N-nitrosodimethylamine (NDMA). Spiramycin (≤ 10 mg/L) could be completely removed within 20 min under the conditions of an initial pH of 4.0, a nZVI dose of 0.02 g/L and a PAA dose of 3.0 mg/L; additionally, 95.8% and 78.8% of PAA and H2O2 were consumed during the process. Electron paramagnetic resonance analysis and quenching experiments confirmed that 52.4% and 44.8% of spiramycin removal was contributed by hydroxyl radical (•OH) and carbon-centered radicals (R-C•), respectively; and Fe2+ released from nZVI played a critical role in radicals generation. Four degradation pathways of spiramycin were proposed and verified by the density of functional theory analysis. 65.2% of the NDMA formation potential (FP) was reduced after the reaction, and its residual was mainly contributed by the undegraded intermediate of dimethylamine. The results of multiple characterizations and continuous degradation experiments indicated that nZVI was stable in the system as the removal of spiramycin was hardly influenced even if reused three times. The nZVI/UV/PAA process is a promising advanced oxidation technology not only for the removal of refractory NDMA precursors (such as spiramycin) but also for significantly lowering the NDMA FP.

N-Nitrosodimethylamine (NDMA) Formation from Ranitidine Impurities: Possible Root Causes of the Presence of NDMA in Ranitidine Hydrochloride.

N-Nitrosodimethylamine (NDMA) is a probable human carcinogen. This study investigated the root cause of the presence of NDMA in ranitidine hydrochloride. Forced thermal degradation studies of ranitidine hydrochloride and its inherent impurities (Imps. A, B, C, D, E, F, G, H, I, J, and K) listed in the European and United States Pharmacopeias revealed that in addition to ranitidine, Imps. A, C, D, E, H, and I produce NDMA at different rates in a solid or an oily liquid state. The rate of NDMA formation from amorphous Imps. A, C, and E was 100 times higher than that from crystalline ranitidine hydrochloride under forced degradation at 110 °C for 1 h. Surprisingly, crystalline Imp. H, bearing neither the N,N-dialkyl-2-nitroethene-1,1-diamine moiety nor a dimethylamino group, also generated NDMA in the solid state, while Imp. I, as an oily liquid, favorably produced NDMA at moderate temperatures (e.g., 50 °C). Therefore, strict control of the aforementioned specific impurities in ranitidine hydrochloride during manufacturing and storage allows appropriate control of NDMA in ranitidine and its pharmaceutical products. Understanding the pathways of the stability related NDMA formation enables improved control of the pharmaceuticals to mitigate this risk.

Degradation of ranitidine and changes in N-nitrosodimethylamine formation potential by advanced oxidation processes: Role of oxidant speciation and water matrix

This study investigated the effects of thirteen (photo/electro) chemical oxidation processes on the formation potential (FP) of N-nitrosodimethylamine (NDMA) during the chloramination of ranitidine in reverse osmosis (RO) permeate and brine. The NDMA-FP varied significantly depending on the pretreatment process, initial pH, and water matrix types. At higher initial pH values (> 7.0), most pretreatments did not reduce the NDMA-FP, presumably because few radical species and more chloramine-reactive byproducts were generated. At pH < 7.0, however, electrochemical oxidation assisted by chloride and Fe2+/H2O2, catalytic wet peroxide oxidation and peroxydisulfate-induced pretreatments removed up to 85% of NDMA-FP in the RO brine. Ultraviolet (UV) irradiation or prechlorination alone did not reduce the NDMA-FP effectively, but combined UV/chlorine treatment effectively reduced the NDMA-FP. In contrast, after UV irradiation (2.1 mW cm−2 for 0.5 h) in the presence of H2O2 and chloramine, NDMA formation increased substantially (up to 26%) during the post-chloramination of the RO permeate. Mass spectrometric analysis and structural elucidation of the oxidation byproducts indicated that compared with the reactive nitrogen species generated by UV/NH2Cl, sulfate radicals and (photo/electro)chemically generated reactive chlorine species were more promising for minimizing NDMA-FP. Unlike, the hemolytic •OH driven by UV/H2O2, the •OH from Fe(IV)-assisted pretreatments showed a significant synergistic effect on NDMA-FP reduction. Overall, the results suggest the need for a careful assessment of the type of radical species to be used for treating an RO water system containing amine-functionalized compounds.

UV-induced activation of organic chloramine: Radicals generation, transformation pathway and DBP formation

Organic chloramines of little disinfection efficacy commonly exist in disinfection process (chlor(am)ination) due to the wide presence of organic amines in water, of which N-chlorodimethylamine (CDMA) is a typical one. For the first time, UV photolysis for the activation of CDMA was investigated. UV photolysis caused the cleavage of N-Cl bond in CDMA to form Cl• and subsequently HO•, both of which are dominant contributors to the destruction of model contaminant bisphenol A (BPA). Typical spectra of HO• were detected by electron paramagnetic resonance (EPR) experiments, while spectra of reactive nitrogen species (RNS) were not detected during UV photolysis of CDMA. The increase of pH (6.0–8.0), HCO3−/CO32−, Cl− and nature organic matter inhibited the degradation of BPA. We proposed pathways of CDMA and BPA degradation based on the identified transformation products. UV photolysis of CDMA and BPA reduced the formation of N-nitrosodimethylamine (NDMA) at pH 8.0, but increased the formation of trichloronitromethane (TCNM) at pH 7.0 and 8.0. The increasing toxicity and the formation of TCNM and NDMA gave us a hint that formation of organic chloramines should be concerned.