Development and validation of high-performance liquid chromatography-Orbitrap mass spectrometric method for quantification of NDMA in ranitidine drug products and evaluation of antioxidants as inhibitors of classical nitrosation reaction.

RATIONALE: N-Nitroso dimethylamine (NDMA) is a mutagenic impurity detected in several ranitidine products. The amino functional group of ranitidine is a risk factor for classical nitrosation-induced NDMA formation in ranitidine drug products during storage conditions. The United States Food and Drug Administration (US FDA) recommended the use of antioxidants to control NDMA in drug products. Considering the need for sensitive analytics, a liquid chromatography/high-resolution mass spectrometry (LC-HRMS) method was developed and validated to detect NDMA in this pilot study to demonstrate the antioxidants as inhibitors of nitrosation reactions. METHODS: The method, utilizing an EC-C18 column and tuned to atmospheric pressure chemical ionization/selected ion monitoring (APCI/SIM) mode, separated NDMA (m/z: 75.0553; tR: 3.71 min) and ranitidine (m/z: 315.1485; tR: 8.61 min). APCI mode exhibited four times higher sensitivity to NDMA than electrospray ionization (ESI) mode. Classical nitrosation of the dimethyl amino group of ranitidine was studied with sodium nitrite in solid pellets. Antioxidants (alpha-tocopherol, ascorbic acid, and trolox) were evaluated as NDMA attenuators in ranitidine pellets under vulnerable storage conditions. The developed method quantified NDMA levels in samples, extracted with methanol through vortex shaking for 45 min. RESULTS: The method achieved a limit of detection (LOD) and limit of quantitation (LOQ) of 0.01 and 0.05 ng/mL, respectively, with linearity within 1-5000 ng/mL (R1: 0.9995). It demonstrated good intra-day and inter-day precision (% RSD [relative standard deviation]: <2) and accuracy (96.83%-101.72%). Nitrosation of ranitidine induced by nitrite was significant (p < 0.001; R2 = 0.9579) at various sodium nitrite levels. All antioxidants efficiently attenuated NDMA formation during ranitidine nitrosation. Ascorbic acid exhibited the highest NDMA attenuation (96.98%), followed by trolox (90.58%). This study recommends 1% ascorbic acid and trolox as potent NDMA attenuators in ranitidine drug products. CONCLUSIONS: This study compared the effectiveness of antioxidants as NDMA attenuators in ranitidine under storage conditions susceptible to NDMA generation. The study concluded that ascorbic acid and trolox are potent inhibitors of NDMA formation and nitrosation attenuators in ranitidine drug products.

Closing Dichloramine Decomposition Nitrogen and Oxygen Mass Balances: Relative Importance of End-Products from the Reactive Nitrogen Species Pathway.

In drinking water chloramination, monochloramine autodecomposition occurs in the presence of excess free ammonia through dichloramine, the decay of which was implicated in N-nitrosodimethylamine (NDMA) formation by (i) dichloramine hydrolysis to nitroxyl which reacts with itself to nitrous oxide (N2O), (ii) nitroxyl reaction with dissolved oxygen (DO) to peroxynitrite or mono/dichloramine to nitrogen gas (N2), and (iii) peroxynitrite reaction with total dimethylamine (TOTDMA) to NDMA or decomposition to nitrite/nitrate. Here, the yields of nitrogen and oxygen-containing end-products were quantified at pH 9 from NHCl2 decomposition at 200, 400, or 800 µeq Cl2·L-1 with and without 10 µM-N TOTDMA under ambient DO (∼500 µM-O) and, to limit peroxynitrite formation, low DO (≤40 µM-O). Without TOTDMA, the sum of free ammonia, monochloramine, dichloramine, N2, N2O, nitrite, and nitrate indicated nitrogen recoveries ±95% confidence intervals were not significantly different under ambient (90 ± 6%) and low (93 ± 7%) DO. With TOTDMA, nitrogen recoveries were less under ambient (82 ± 5%) than low (97 ± 7%) DO. Oxygen recoveries under ambient DO were 88-97%, and the so-called unidentified product of dichloramine decomposition formed at about three-fold greater concentration under ambient compared to low DO, like NDMA, consistent with a DO limitation. Unidentified product formation stemmed from peroxynitrite decomposition products reacting with mono/dichloramine. For a 2:2:1 nitrogen/oxygen/chlorine atom ratio and its estimated molar absorptivity, unidentified product inclusion with uncertainty may close oxygen recoveries and increase nitrogen recoveries to 98% (ambient DO) and 100% (low DO).

New Perspectives on the Interactions between Adsorption and Degradation of Organic Micropollutants in Granular Activated Carbon Filters.

The removal of organic micropollutants in granular activated carbon (GAC) filters can be attributed to adsorption and biological degradation. These two processes can interact with each other or proceed independently. To illustrate the differences in their interaction, three 14C-labeled organic micropollutants with varying potentials for adsorption and biodegradation were selected to study their adsorption and biodegradation in columns with adsorbing (GAC) and non-adsorbing (sand) filter media. Using 14CO2 formation as a marker for biodegradation, we demonstrated that the biodegradation of poorly adsorbing N-nitrosodimethylamine (NDMA) was more sensitive to changes in the empty bed contact time (EBCT) compared with that of moderately adsorbing diclofenac. Further, diclofenac that had adsorbed under anoxic conditions could be degraded when molecular oxygen became available, and substantial biodegradation (≥60%) of diclofenac could be achieved with a 15 min EBCT in the GAC filter. These findings suggest that the retention of micropollutants in GAC filters, by prolonging the micropollutant residence time through adsorption, can enable longer time periods for degradations than what the hydraulic retention time would allow for. For the biologically recalcitrant compound carbamazepine, differences in breakthrough between the 14C-labeled and nonradiolabeled compounds revealed a substantial retention via successive adsorption-desorption, which could pose a potential challenge in the interpretation of GAC filter performance.

Comparative Evaluation of Chemical and Photolytic Denitrosation Methods for Chemiluminescence Detection of Total N-Nitrosamines in Wastewater Samples.

N-Nitrosamines form as byproducts during oxidative water treatment and occur as impurities in consumer and industrial products. To date, two methods based on chemiluminescence (CL) detection of nitric oxide liberated from N-nitrosamines via denitrosation with acidic triiodide (HI3) treatment or ultraviolet (UV) photolysis have been developed to enable the quantification of total N-nitrosamines (TONO) in environmental water samples. In this work, we configured an integrated experimental setup to compare the performance of HI3-CL and UV-CL methods with a focus on their applicability for TONO measurements in wastewater samples. With the use of a large-volume purge vessel for chemical denitrosation, the HI3-CL method achieved signal stability and detection limits comparable to those achieved by the UV-CL method which utilized a microphotochemical reactor for photolytic denitrosation. Sixty-six structurally diverse N-nitroso compounds (NOCs) yielded a range of conversion efficiencies relative to N-nitrosodimethylamine (NDMA) regardless of the conditions applied for denitrosation. On average, TONO measured in preconcentrated raw and chloraminated wastewater samples by the HI3-CL method were 2.1 ± 1.1 times those measured by the UV-CL method, pointing to potential matrix interferences as further confirmed by spike recovery tests. Overall, our comparative assessment of the HI3-CL and UV-CL methods serves as a basis for addressing methodological gaps in TONO analysis.

Occurrence of N-nitrosodimethylamine in roasted Alaska pollock fillets during processing and storage and preliminary cancer risk assessment.

BACKGROUND: Dried and salt-fermented fish products are important sources of N-nitrosodimethylamine (NDMA) exposure for human. As a potent carcinogen, NDMA was frequently detected in roasted Alaska pollock fillet products (RPFs), which is among the most common fish products in China. Until now, the occurrence and development of NDMA and its precursors (nitrites, nitrates and dimethylamine) in RPFs during processing and storage were not well elucidated, and safety evaluation of this fish product is also urgently needed. RESULTS: The presence of precursors in the raw material was verified and significant increase of nitrates and nitrites during processing was observed. NDMA was found generated during pre-drying (3.7 µg kg-1 dry basis) and roasting (14.6 µg kg-1 dry basis) process. Continuous increase in NDMA content can also be found during storage, especially at higher storage temperature. The 95th percentile of Monte Carlo simulated cancer risk (3.73 × 10-5 ) surpassed the WHO threshold (1.00 × 10-5 ) and sensitivity analysis implies the risk was mainly attributable to NDMA level in RPFs. CONCLUSION: The occurrence of NDMA in RFPs was mainly a result of endogenous factors originating in Alaska pollock during processing and storage rather than exogenous contamination, and temperature played a pivotal role. The preliminary risk assessment results suggest that long-term consumption of RPFs would impose potential health risks for consumers. © 2023 Society of Chemical Industry.

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 (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.

Temperature-Dependent Formation of N-Nitrosodimethylamine during the Storage of Ranitidine Reagent Powders and Tablets.

The purpose of this study was to elucidate the effect of high-temperature storage on the stability of ranitidine, specifically with respect to the potential formation of N-nitrosodimethylamine (NDMA), which is classified as a probable human carcinogen. Commercially available ranitidine reagent powders and formulations were stored under various conditions, and subjected to LC-MS/MS analysis. When ranitidine tablets from two different brands (designated as tablet A and tablet B) were stored under accelerated condition (40 °C with 75% relative humidity), following the drug stability guidelines issued by the International Conference on Harmonisation (ICH-Q1A), for up to 8 weeks, the amount of NDMA in them substantially increased from 0.19 to 116 ppm and from 2.89 to 18 ppm, respectively. The formation of NDMA that exceeded the acceptable daily intake limit (0.32 ppm) at the temperature used under accelerated storage conditions clearly highlights the risk of NDMA formation in ranitidine formulations when extrapolated to storage under ambient conditions. A forced-degradation study under the stress condition (60 °C for 1 week) strongly suggested that environmental factors such as moisture and oxygen are involved in the formation of NDMA in ranitidine formulations. Storage of ranitidine tablets and reagent powders at the high temperatures also increased the amount of nitrite, which is considered one of the factors influencing NDMA formation. These data indicate the necessity of controlling/monitoring stability-related factors, in addition to controlling impurities during the manufacturing process, in order to mitigate nitrosamine-related health risks of certain pharmaceuticals.

N-Nitrosodimethylamine Contamination in the Metformin Finished Products.

A GC-MS/MS method with EI ionization was developed and validated to detect and quantify N-nitrosodimethylamine (NDMA) and seven other nitrosamines in 105 samples of metformin tablets from 13 different manufactures. Good linearity for each compound was demonstrated over the calibration range of 0.5-9.5 ng/mL. The assay for all substances was accurate and precise. NDMA was not detected in the acquired active pharmaceutical ingredient (API); however, NDMA was detected in 64 (85.3%) and 22 (91.7%) of the finished product and prolonged finished product samples, respectively. European Medicines Agency recommends the maximum allowed limit of 0.032 ppm in the metformin products. Hence, 28 finished products and 7 pronged dosage products were found to exceed the acceptable limit of daily intake of NDMA contamination. The implications of our findings for the testing of pharmaceutical products are discussed.

Reversible photochromic photocatalyst Bi2O3/TiO2/Al2O3 with enhanced visible photoactivity: application toward UDMH degradation in wastewater.

1,1-Dimethylhydrazine (UDMH) and its by-products were considered carcinogenic toxins and represent a serious health hazard to the population once present in water under natural conditions without treatment. The conventional degradation method suffers from incomplete removal of intermediate products (especially N-nitrosodimethylamine (NDMA)), the powdery catalysis being difficult to recover and results in high energy consumption. In this study, a series of Bi2O3/TiO2/Al2O3 (BTA) photocatalysts have been successfully synthesized by a simple dry mixing method with powder material followed by their immobilization. It was evaluated by the photocatalytic degradation of UDMH present in wastewater, which can be recovered by rapid filtration and utilizes only solar energy. The catalyst exhibited markedly enhanced photocatalytic activity for the degradation of UDMH wastewater compared with conventional TiO2/Al2O3 (TA) catalysts under UV, visible and solar irradiation. Besides, the intermediate NDMA was gradually completely degraded. The photocatalysts were extensively characterized using scanning electron microscopy, energy dispersive spectrometry, specific surface area (BET), X-ray diffraction, X-ray photoelectron spectroscopy, UV-visible diffuse reflectance spectroscopy and photo-electrochemical I-t curves evaluation. The results revealed that all the BTA composites exhibited high stability and stronger absorbance in visible light. In addition, the BTA exhibited a reversible photochromic property that can effectively expand the range of light absorption and enhance the photocatalytic activity. The reversible photochromic properties of BTA explained in the proposed mechanism model are expected to be useful for detecting and sensing UDMH or other organic contaminants.

Oxidation of Citalopram with Sodium Hypochlorite and Chlorine Dioxide: Influencing Factors and NDMA Formation Kinetics.

The highly prescribed antidepressant, citalopram, as one of newly emerging pollutants, has been frequently detected in the aquatic environment. Citalopram oxidation was examined during sodium hypochlorite (NaOCl) and chlorine dioxide (ClO2) chlorination processes since conventional wastewater treatment plants cannot remove citalopram effectively. Citalopram has been demonstrated to form N-nitrosodimethylamine (NDMA) during chlorination in our previous study. Further investigation on NDMA formation kinetics was conducted in the present study. Influences of operational variables (disinfectant dose, pH value) and water matrix on citalopram degradation, as well as NDMA generation, were evaluated. The results indicated high reactivity of citalopram with NaOCl and ClO2. NDMA formation included two stages during CIT oxidation, which were linear related with reaction time. NaOCl was more beneficial to remove CIT, but it caused more NDMA formation. Increasing disinfectant dosage promoted citalopram removal and NDMA formation. However, no consistent correlation was found between citalopram removal and pH. Contrary to the situation of citalopram removal, NDMA generation was enhanced when citalopram was present in actual water matrices, especially in secondary effluent. DMA, as an intermediate of citalopram chlorination, contributed to NDMA formation, but not the only way.

Determination of acid dissociation constants and reaction kinetics of dimethylamine-based PPCPs with O3, NaClO, ClO2 and KMnO4.

Dimethylamine-based pharmaceutical personal care products (DMA-based PPCPs) are a group of N-nitrosodimethylamine (NDMA) precursors. The acid dissociation constant (pKa) values of four DMA-based PPCPs were determined by potentiometric titration over the pH range of 3-11. The pKa values of ranitidine, nizatidine, doxylamine and carbinoxamine corresponding to the DMA moiety were 8.4, 6.8, 9.4 and 9.1, respectively. Competition reaction kinetics and pseudo-first-order reaction kinetics were used to determine the reaction rate constant (k) of the DMA-based PPCPs with O3, NaClO, ClO2 and KMnO4. Comparing the degradation rate constants of the four DMA-based PPCPs, the results of ClO2 oxidation were close, and for the other three oxidants, the order was kranitidine ≈ knizatidine > kdoxylamine ≈ kcarbinoxamine. Comparing the reaction rate of the four oxidants, for ranitidine and nizatidine, the order was kNaClO > kO3 > kKMnO4 > kClO2, and for doxylamine and carbinoxamine, the order was kO3 > kNaClO > kClO2 > kKMnO4.

The effect of ethanol and N-nitrosodimethylamine on the iNOS-dependent NO production in human neutrophils. Role of NF-κB.

1. The objective of study was to determine the influence of ethanol and/or N-nitrosodimethyloamine (NDMA) on the inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production by human neutrophils and determination of the role of NF-κB in this process. 2. Isolated polymorphonuclear leukocytes (PMNs) derived from 15 human volunteers were incubated in the presence of ethanol and/or NDMA. Expression of the tested proteins were evaluated using the Western blot method. Total NO metabolites was assayed in the cell cultures by Griess reaction. 3. In neutrophils exposed to ethanol or NDMA was observed an increased NF-κB-dependent NO production mediated by iNOS with the contribution of MAP kinases: p38 and JNK. An inhibiting effect of NF-κB signaling pathway on the MAP kinases was observed, which are involved in the iNOS-dependent NO production. By the simultaneous effect, ethanol and NDMA caused stronger generation of NO by neutrophils without the contribution of iNOS. Inhibition of NF-κB in cells simultaneously exposed to the xenobiotics caused a decreased expression of MAP kinases. 4. Individual and simultaneous effect of ethanol and NDMA may cause disorders in the response of immune system. However, the joint effect of the tested substances results in uncontrolled interactions, leading to cascading disorders of signal transduction.

Mechanistic Insight into the Degradation of Nitrosamines via Aqueous-Phase UV Photolysis or a UV-Based Advanced Oxidation Process: Quantum Mechanical Calculations.

Nitrosamines are a group of carcinogenic chemicals that are present in aquatic environments that result from byproducts of industrial processes and disinfection products. As indirect and direct potable reuse increase, the presence of trace nitrosamines presents challenges to water infrastructures that incorporate effluent from wastewater treatment. Ultraviolet (UV) photolysis or UV-based advanced oxidation processes that produce highly reactive hydroxyl radicals are promising technologies to remove nitrosamines from water. However, complex reaction mechanisms involving radicals limit our understandings of the elementary reaction pathways embedded in the overall reactions identified experimentally. In this study, we perform quantum mechanical calculations to identify the hydroxyl radical-induced initial elementary reactions with N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine, and N-nitrosomethylbutylamine. We also investigate the UV-induced NDMA degradation mechanisms. Our calculations reveal that the alkyl side chains of nitrosamine affect the reaction mechanism of hydroxyl radicals with each nitrosamine investigated in this study. Nitrosamines with one- or two-carbon alkyl chains caused the delocalization of the electron density, leading to slower subsequent degradation. Additionally, three major initial elementary reactions and the subsequent radical-involved reaction pathways are identified in the UV-induced NDMA degradation process. This study provides mechanistic insight into the elementary reaction pathways, and a future study will combine these results with the kinetic information to predict the time-dependent concentration profiles of nitrosamines and their transformation products.

Effect of ozonation on minocycline degradation and N-Nitrosodimethylamine formation.

The objective of this study was to assess reactivity of Minocycline (MNC) towards ozone and determine the effects of ozone dose, pH value, and water matrix on MNC degradation as well as to characterize N-Nitrosodimethylamine (NDMA) formation from MNC ozonation. The MNC initial concentration of the solution was set in the range of 2-20 mg/L to investigate NDMA formation during MNC ozonation. Four ozone doses (22.5, 37.2, 58.0, and 74.4 mg/min) were tested to study the effect of ozone dose. For the evaluation of effects of pH value, pH was adjusted from 5 to 9 in the presence of phosphate buffer. MNC ozonation experiments were also conducted in natural water to assess the influence of water matirx. The influence of the typical component of natural water was also investigated with the addition of HA and NaHCO3 solution. Results indicated that ozone was effective in MNC removal. Consequently, NDMA and dimethylamine (DMA) were generated from MNC oxidation. Increasing pH value enhanced MNC removal but led to greater NDMA generation. Water matrices, such as HCO3- and humic acid, affected MNC degradation. Conversely, more NDMA accumulated due to the inhibition of NDMA oxidation by oxidant consumption. Though ⋅OH can enhance MNC degradation, ozone molecules were heavily involved in NDMA production. Seven transformation products were identified. However, only DMA and the unidentified tertiary amine containing DMA group contributed to NDMA formation.

Reduction by enhanced coagulation of dissolved organic nitrogen as a precursor of N-nitrosodimethylamine.

Raw water from the Banglen (BL) water treatment plant (WTP) and Bangkhen (BK) WTP in central Thailand and Hatyai (HY) WTP in southern Thailand was investigated for dissolved organic nitrogen (DON) reduction. The DON(mg N/L) and the dissolved organic carbon (DOC)/DON ratio were 0.34 and 21, 0.24 and 18, and 1.12 and 3 for the raw waters from BL, BK, and HY WTPs, respectively. Polyaluminum chloride (PACl) dosages of 150, 80, and 40 mg/L at pH 7 were the optimal coagulation conditions for the raw waters from BL, BK, and HY WTPs, respectively, and could reduce DON by 50%, 42%, and 42%, respectively. PACl and powder activated carbon (PAC, both in mg/L) at 150 and 20, 80 and 20, and 40 and 60 could reduce DON in the raw waters from BL, BK, and HY WTPs by 71%, 67%, and 29%, respectively. DOC/DON values of water treated with PACl were similar to those of raw water. DOC/DON values of water treated with PACl and PAC were lower than those of raw water. N-nitrosodimethylamine (NDMA) formation potentials of raw water, water treated with PACl, or both PACl and PAC, and organic fractions of BL, BK, and HY WTPs were below the detection limits of 542 and 237 ng/L, respectively. Reductions in fluorescence intensities of tryptophan-like substances at peaks 240/350 and 280/350 (nmEx/nmEm) were moderately (correlation coefficient, R = 0.85 and 0.86) and fairly (R = 0.59, 0.67, and 0.75) correlated with DON reduction.

Capability of cation exchange technology to remove proven N-nitrosodimethylamine precursors.

N-nitrosodimethylamine (NDMA) precursors consist of a positively charged dimethylamine group and a non-polar moiety, which inspired us to develop a targeted cation exchange technology to remove NDMA precursors. In this study, we tested the removal of two representative NDMA precursors, dimethylamine (DMA) and ranitidine (RNTD), by strong acidic cation exchange resin. The results showed that pH greatly affected the exchange efficiency, with high removal (DMA>78% and RNTD>94%) observed at pHMg2+>RNTD+>K+>DMA+>NH4+>Na+. The partition coefficient of DMA+ to Na+ was 1.41±0.26, while that of RNTD+ to Na+ was 12.1±1.9. The pseudo second-order equation fitted the cation exchange kinetics well. Bivalent inorganic cations such as Ca2+ were found to have a notable effect on NA precursor removal in softening column test. Besides DMA and RNTD, cation exchange process also worked well for removing other 7 model NDMA precursors. Overall, NDMA precursor removal can be an added benefit of making use of cation exchange water softening processes.

Characterization of N-nitrosodimethylamine formation from the ozonation of ranitidine.

N-nitrosodimethylamine (NDMA) is an emerging disinfection by-product which is formed during water disinfection in the presence of amine-based precursors. Ranitidine, as one kind of amine-based pharmaceuticals, has been identified as NDMA precursor with high NDMA molar conversion during chloramination. This study focused on the characterization of NDMA formation during ozonation of ranitidine. Influences of operational variables (ozone dose, pH value) and water matrix on NDMA generation as well as ranitidine degradation were evaluated. The results indicate high reactivity of ranitidine with ozone. Dimethylamine (DMA) and NDMA were generated due to ranitidine oxidation. High pH value caused more NDMA accumulation. NDMA formation was inhibited under acid conditions (pH≤5) mainly due to the protonation of amines. Water matrix such as HCO3- and humic acid impacted NDMA generation due to OH scavenging. Compared with OH, ozone molecules dominated the productions of DMA and NDMA. However, OH was a critical factor in NDMA degradation. Transformation products of ranitidine during ozonation were identified using gas chromatography-mass spectrometry. Among these products, just DMA and N,N-dimethylformamide could contribute to NDMA formation due to the DMA group in the molecular structures. The NDMA formation pathway from ranitidine ozonation was also proposed.

Structural Modifications to Quaternary Ammonium Polymer Coagulants to Inhibit N-Nitrosamine Formation.

Quaternary ammonium cationic polymers, such as poly(diallyldimethylammonium chloride) (polyDADMAC) and epichlorohydrin-dimethylamine (Epi-DMA), are commonly used by water utilities to enhance removal of particles and dissolved organic matter (DOM) from raw waters. Unfortunately, chloramination of waters treated with quaternary ammonium polymers leads to the formation of carcinogenic N-nitrosodimethylamine (NDMA). In this study, two approaches were developed to modify polyDADMAC and Epi-DMA to inhibit N-nitrosamine formation. The first approach involved treatment of polymers with methyl iodide (MeI), an alkylating agent, to convert polymer-bound tertiary amine groups to less chloramine-reactive quaternary ammonium groups. The second approach involved synthesis of polymers bearing less chloramine-reactive quaternary ammonium groups with dipropylamino (DPA) substituents. Treatment with MeI reduced NDMA formation from polymers by ∼75%, while synthesis of DPA-based polymers eliminated NDMA formation and formed N-nitrosodipropylamine, which is 10-fold less carcinogenic than NDMA, at 20-fold lower yields. Bench-scale jar tests demonstrated that both MeI-treated and DPA-based polymers achieved similar removal of particles and DOM as the original polyDADMAC and Epi-DMA at both low and high doses, but formed significantly less N-nitrosamines. This work demonstrates two approaches for modifying quaternary ammonium cationic polymers, which may enable water utilities to meet potential future regulations on N-nitrosamines while maintaining polymer usage to meet existing regulations.

Organic Contaminant Abatement in Reclaimed Water by UV/H2O2 and a Combined Process Consisting of O3/H2O2 Followed by UV/H2O2: Prediction of Abatement Efficiency, Energy Consumption, and Byproduct Formation.

UV/H2O2 processes can be applied to improve the quality of effluents from municipal wastewater treatment plants by attenuating trace organic contaminants (micropollutants). This study presents a kinetic model based on UV photolysis parameters, including UV absorption rate and quantum yield, and hydroxyl radical (·OH) oxidation parameters, including second-order rate constants for ·OH reactions and steady-state ·OH concentrations, that can be used to predict micropollutant abatement in wastewater. The UV/H2O2 kinetic model successfully predicted the abatement efficiencies of 16 target micropollutants in bench-scale UV and UV/H2O2 experiments in 10 secondary wastewater effluents. The model was then used to calculate the electric energies required to achieve specific levels of micropollutant abatement in several advanced wastewater treatment scenarios using various combinations of ozone, UV, and H2O2. UV/H2O2 is more energy-intensive than ozonation for abatement of most micropollutants. Nevertheless, UV/H2O2 is not limited by the formation of N-nitrosodimethylamine (NDMA) and bromate whereas ozonation may produce significant concentrations of these oxidation byproducts, as observed in some of the tested wastewater effluents. The combined process of O3/H2O2 followed by UV/H2O2, which may be warranted in some potable reuse applications, can achieve superior micropollutant abatement with reduced energy consumption compared to UV/H2O2 and reduced oxidation byproduct formation (i.e., NDMA and/or bromate) compared to conventional ozonation.