Characterization of New Nitrosamines in Drinking Water Using Liquid

Nov 8, 2006 - Environmental Mass Spectrometry: Emerging Contaminants and Current Issues. Susan D. Richardson. Analytical Chemistry 2008 80 (12), 4373-...
3 downloads 12 Views 149KB Size
Download PDF
Environ. Sci. Technol. 2006, 40, 7636-7641

Characterization of New Nitrosamines in Drinking Water Using Liquid Chromatography Tandem Mass Spectrometry YUAN-YUAN ZHAO, JESSICA BOYD, STEVE E. HRUDEY, AND XING-FANG LI* Environmental Health Sciences, School of Public Health and Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, 10-102 Clinical Sciences Building, Edmonton, Alberta, Canada T6G 2G3

N-Nitrosodimethylamine (NDMA), a member of a group of probable human carcinogens, has been detected as a disinfection byproduct (DBP) in drinking water supplies in Canada and the United States. To comprehensively investigate the occurrence of possible nitrosamines in drinking water supplies, a liquid chromatography-tandem mass spectrometry technique was developed to detect both thermally stable and unstable nitrosamines. This technique consisted of solid-phase extraction (SPE), liquid chromatography (LC) separation, and tandem quadrupole linear ion trap mass spectrometry (MS/MS) detection. It enabled the determination of sub-ng/L levels of nine nitrosamines. Isotope-labeled N-nitrosodimethylamine-d6 (NDMA-d6) was used as the surrogate standard for determining recovery, and N-nitrosodi-n-propylamine-d14 (NDPA-d14) was used as the internal standard for quantification. The method detection limits were estimated to be 0.1-10.6 ng/L, and the average recoveries were 41-111% for the nine nitrosamines; of these, NDMA, N-nitrosopyrrolidine (NPyr), N-nitrosopiperidine (NPip), and N-nitrosodiphenylamine (NDPhA) were identified and quantified in drinking water samples collected from four locations within the same distribution system. In general, the concentrations of these four nitrosamines in this distribution system increased with increasing distance from the water treatment plant, indicating that the amount of formation was greater than the amount of decomposition within this time frame. The identification of NPip and NDPhA in drinking water systems and the distribution profiles of these nitrosamines have not been reported previously. These nitrosamines are toxic, and their presence as DBPs in drinking water may have toxicological relevance.

Introduction The disinfection of drinking water has resulted in the dramatic reduction and elimination of waterborne diseases, such as cholera and typhoid (1). It is essential for the protection of public health to perform and maintain proper water disinfection processes. However, unintended disinfection byproducts (DBPs) are produced because the disinfectants themselves, such as chlorine, chloramines, and chlorine dioxide, * Corresponding author phone: (780)492-5094; fax: (780)492-7800; e-mail: [email protected]. 7636

9

ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 40, NO. 24, 2006

can react with naturally occurring materials in the water. Over 600 DBPs have been reported (2-4). Most research on DBPs has focused on regulated DBPs, which include trihalomethanes (THMs), haloacetic acids (HAAs), bromate, and chlorite (3). However, the existing epidemiological studies on these known DBPs have failed to produce a truly plausible toxicological explanation for the relative cancer risk and adverse health effects estimated. It is suspected that many other unidentified DBPs may play more important roles in the adverse health effects observed. A number of new DBPs such as halonitromethanes and iodoacids have been identified, and their cytotoxicity and genotoxicity in mammalian cells have been found to be much higher than those of the regulated DBPs (4-6). These studies demonstrate that some previously unidentified DBPs may be more toxicologically relevant than the regulated DBPs. N-Nitrosodimethylamine (NDMA), a probable human carcinogen (7), was first detected as a DBP in ON, Canada, and in CA, U.S.A. (8, 9). As a result, Ontario has established a drinking water quality standard of 9 ng/L for NDMA (10), while California has set a notification level of 10 ng/L for NDMA (9). The United States Environmental Protection Agency (EPA) has classified some nitrosamines as probable human carcinogens (7, 11). EPA has also included six nitrosamines in the proposed unregulated contaminant monitoring rule (12). NDMA has been proven to be a water contaminant (8, 9, 12-14); however, little is known about the occurrence and formation of other nitrosamines in drinking water systems. Analysis of trace levels of nitrosamines in water requires extraction/preconcentration. Solid-phase extraction (SPE) methods are often used for preconcentration of nitrosamines (15). Excellent NDMA recoveries (>87%) have been obtained using LiChrolut EN and Ambersorb-572 as packing materials (16). Recent progress on the analysis of DBPs has been summarized in several reviews (3, 17-20). Gas chromatography-mass spectrometry (GC/MS) techniques with electron impact (EI) or chemical ionization (CI) and GC with thermal energy analyzer (TEA) (8, 16, 21-26) are used for analysis of nitrosamines, but these methods are limited to analysis of volatile and thermally stable compounds. They also do not provide sufficient structural information for identification of unknown DBPs. EPA method 521 uses GC/MS/MS to detect NDMA and six other nitrosamines in drinking water (27), but it cannot detect thermally labile nitrosamines. Liquid chromatography (LC) and capillary electrophoresis (CE) with UV, fluorescence, and MS/MS detection methods have also been reported, but they are mainly designed for a few specific nitrosamines in tobacco (28-37). No LC-MS/MS method is currently available for analysis of low ng/L levels of a variety of nitrosamines in drinking water. In order to characterize possible nitrosamines in drinking water, we developed a method combining SPE enrichment and microcolumn LC separation with tandem mass spectrometry using multiple reaction monitoring (MRM). The initial target N-nitrosamines (Supporting Information Figure S1) were NDMA, N-nitrosomethylethylamine (NMEA), Nnitrosodiethylamine (NDEA), N-nitrosodi-n-propylamine (NDPA), N-nitrosomorpholine (NMor), N-nitrosopyrrolidine (NPyr), N-nitrosopiperidine (NPip), N-nitrosodi-n-butylamine (NDBA), and N-nitrosodiphenylamine (NDPhA). We demonstrated that the SPE-LC-MS/MS (MRM) method sensitively detected both GC-detectable and GC-undetectable nitrosamines. With this method we were able to study the 10.1021/es061332s CCC: $33.50

 2006 American Chemical Society Published on Web 11/08/2006

occurrence and distribution of different nitrosamines in drinking water systems.

Experimental Section Reagents. A standard solution (10 µg/mL each) containing the nine nitrosamines, NDMA, NMEA, NPyr, NPip, NMor, NDEA, NDPA, NDBA, and NDPhA, was purchased from Supelco (Oakville, ON, Canada). Isotope-labeled standards ([6-H2] N-nitrosodimethylamine, NDMA-d6, and [14-H2] N-nitrosodi-n-propylamine, NDPA-d14) (98%) were obtained from Cambridge Isotope Laboratories (Andover, MA). Methanol (AnalR grade) and dichloromethane (Omni-Solv grade) were purchased from VWR International (Mississauga, ON, Canada). Ammonium acetate (ACS reagent grade) and L-ascorbic acid (analytical grade) were supplied by SigmaAldrich (Oakville, ON, Canada). All other chemicals were of analytical grade and obtained from Fisher Scientific (Nepean, ON, Canada) unless otherwise indicated. The SPE packing materials, Ambersorb 572 (Rohm & Hass; Philadelphia, PA) and LiChrolut EN (Merck; Darmstadt, Germany), were obtained from Supelco and VWR International, respectively. Caution: N-Nitrosamines are potential carcinogens for humans and animals. Safety precautions were taken when handling these compounds, and waste disposal followed proper safety procedures. Standard Solutions. A stock solution (1000 µg/mL) containing the nine N-nitrosamines was prepared in methanol and stored at 4 °C. Working solutions (5-200 µg/L) were prepared with 1:1 methanol/water. Each working solution contained the surrogate standard NDMA-d6 (50 µg/L) and the internal standard NDPA-d14 (50 µg/L). All working solutions were freshly prepared prior to LC-MS/MS analysis. The purity and stability of NDMA-d6 were determined by repeated analyses of NDMA-free water spiked with 40 ng/L of NDMA-d6. No NDMA (nonlabeled) was detected using the SPE-LC-MS/MS (MRM) method described below. This confirmed that the NDMA determined was found only in the samples. Extraction of Water Samples. Water samples were collected from four locations within one distribution system, in which surface water was treated by a combination of chloramination and UV irradiation. The sample collection and extraction procedures have been previously described in detail (16). Source water and treated water samples were collected in 1-L amber-glass bottles. Twenty mg/L L-ascorbic acid was added to quench the chlorine residual. Trip blanks were prepared and analyzed along with the drinking water samples. Samples were stored at 4 °C until analysis. The extraction of nitrosamines from the water samples was performed by SPE (16). Briefly, the SPE cartridge was packed with 350 mg of LiChrolut EN (bottom layer), 500 mg of Ambersorb 572 (middle), and glass wool (top). A vacuum system (-30 kpa) was used to draw the water sample through the cartridge. Each packed SPE cartridge was initially rinsed with 15 mL each of hexane and dichloromethane, and the residual organic solvents were removed under vacuum. The SPE cartridges were then conditioned with 15 mL each of methanol and water. One gram of sodium bicarbonate was added to 500 mL of the water sample (∼ pH 8). NDMA-d6 (100 µL of 200 µg/L) was then spiked into the sample (final concentration of 40 ng/L). The sample passed through the SPE cartridge at a flow rate of 3-5 mL/min. The analytes absorbed on the SPE cartridge were eluted using 15 mL of dichloromethane. The organic eluent was collected and concentrated down to 200 µL under a high purity nitrogen stream in a 40 °C water bath. After concentration, the internal standard NDPA-d14 (100 µL of 200 µg/L) was added to the extract (final concentration of 40 ng/L) prior to the LC-MS/ MS analysis. The extracts were stored at 4 °C and analyzed using LC-MS/MS within a week. Nitrosamine-free water

blanks were extracted in each set to ensure all reagents were nitrosamine-free. Water samples spiked with 10 or 40 ng/L each of the nine nitrosamines were also included in each extraction set to ensure accuracy. The surrogate standard, NDMA-d6, was used to determine recovery; the internal standard, NDPA-d14, was used for quantification. The effect of dichloromethane and methanol on analyte elution from the SPE cartridges was also examined when a water (Optima grade) sample spiked with 40 ng/L of NDMAd6 was analyzed. Recovery of NDMA-d6 was 75% when dichloromethane was used as the solvent but only 40% when methanol was the solvent. Therefore, dichloromethane was used to elute the analytes from the SPE cartridge. LC-MS/MS Analysis. An Agilent 1100 capillary liquid chromatograph (Agilent Technologies; Palo Alto, CA) was coupled directly to an API 4000 QTrap mass spectrometer (Applied Biosystems/MDS Sciex; Concord, ON, Canada) with an ionspray ionization source. Analyst software for API 4000 QTrap was used for data acquisition and analysis. A C8 (2) capillary column (150 × 0.32 mm i.d., 5 µm) (Phenomenex; Torrance, CA) was used for separation. The mobile phase was composed of solvent A (10 mM ammonium acetate and 0.01% acetic acid in water (Optima grade)) and solvent B (100% methanol). The solvent gradient program consisted of 60% of solvent B for 1 min, increasing solvent B from 60% to 90% over 5 min, and returning back to 60% of solvent B over 0.1 min, followed by a 13-min re-equilibration prior to the next sample injection. The flow rate was 6 µL/min. The sample injection volume was 1.2 µL. Both ESI and APCI were examined for ionization of the target nitrosamines. The ESI produced characteristic ions of the parent compounds and product ions for all nitrosamines, whereas the APCI could not generate the parent ion of thermally unstable nitrosamines such as NDPhA. The detection of both the parent and product ions is important for the specific determination of nitrosamines at trace concentrations in water. Therefore, ESI was used to interface the LC with the tandem MS. Positive electrospray ionization combined with the multiple-reaction monitoring (MRM) mode was used. The optimization of MS conditions was performed by infusing a mixture of N-nitrosamines (1 µg/mL each in 10 mM ammonium acetate in 90% MeOH: 10% water) using a syringe pump. The optimal ionspray parameters were as follows: curtain gas (N2) at 10, ion-source gas 1 at 13, and ionspray voltage at 4500 V. The declustering potential (DP), collision energy (CE), and cell exit potential (CXP) were optimized for individual analytes (Supporting Information Table S1). Standard solutions of 5-200 µg/L with NDPA-d14 (internal standard, 50 µg/L) and NDMA-d6 (surrogate standard, 50 µg/L) were analyzed. The relative response factors (RRFs) for the nine target nitrosamines and NDMA-d6 were calculated based on the ratio of the relative peak area of the individual analytes to that of NDPA-d14. The reproducibility of RRFs was also determined. Routine quality control measures included the injection of a blank solution consisting of the mobile phase to check for carryover after each sample and a set of standard solutions of 5-200 µg/L to calculate the RRFs of each compound before and after a set of authentic drinking water samples.

Results and Discussion Characterization of Possible Nitrosamine DBPs. In order to achieve the high sensitivity and specificity necessary for detection of possible nitrosamines in drinking water, we have developed a method that incorporates preconcentration by solid-phase extraction (SPE), separation by liquid chromatography (LC), and specific detection by tandem MS with multiple-reaction monitoring (MRM) of the specific parent and product ions. To obtain the parent-product ion pairs for VOL. 40, NO. 24, 2006 / ENVIRONMENTAL SCIENCE & TECHNOLOGY

9

7637

FIGURE 1. Tandem mass spectra of the nine nitrosamines showing their characteristic ions that are used for specific determination of these compounds in water. MRM detection, we first characterized the fragmentation behavior of the nine nitrosamines under tandem MS conditions. Figure 1 shows typical tandem mass spectra of the nine nitrosamines produced under the optimized conditions. The major ions were the parent ion and a product ion that was used as the diagnostic ion. MRM detection of the parent and the product ions provides confirmation of the nitrosamines detected. Therefore, the parent/product ion pairs for each nitrosamine were used for MRM detection to develop the LC-MS/MS method. The specificity of MRM detection for each nitrosamine was further improved using LC separation, which allowed differentiation of interference molecules that could have the same MRM transition as the analyte of interest. Figure 2 shows the chromatograms obtained by monitoring two ion pairs of m/z 131/89 (NDPA) and 199/169 (NDPhA), when the extracts of a spiked pure water sample and an authentic drinking water sample were analyzed. MRM detection of m/z 131/89 (Figure 2A) shows that the NDPA standard is detected at retention time 6.87 min in the pure water sample. The same MRM analysis of the authentic water sample shows a peak at retention time 5.56 min. Spiking the standard in the sample extract confirms that the peak (m/z 131/89) at 5.56 min was not NDPA. Similarly, Figure 2(B) shows that the NDPhA standard (m/z 199/169) spiked in pure water was detected at retention time 7.94 min. However, MRM monitoring of m/z 199/169 detected two peaks at 5.83 and 7.96 min in the authentic water sample extract. The peak at 7.96 min was identified as NDPhA based on the ion pair monitoring and retention time data. The other peak at 5.83 min is clearly separated from NDPhA, confirming that it is not NDPhA, even though it has 7638

9

ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 40, NO. 24, 2006

FIGURE 2. Analysis of extracts of the standards spiked in Optima water sample and a drinking water sample by monitoring of m/z 131/89 (A) and m/z 199/169 (B) showing the separation of NDPA and NDPhA from background interference. The concentration of the standards in the spiked Optima water sample is 5 ng/L each. the same ions of m/z 199/169. These results demonstrate the importance and usefulness of a simple combination of LC separation with MS detection. Although the LC provides only partial separation of these nitrosamines, the retention times provide useful complementary information to MRM monitoring for identification of the analytes in the samples. We further combined the LC-MS/MS (MRM) with SPE preconcentration to determine trace levels of nitrosamines in drinking water. Both GC-detectable (NDMA, NMEA, NDEA, NMor, NPyr, NPip, NDPA, and NDBA) and GC-undetectable (NDPhA) nitrosamines at 40 ng/L in the water sample were successfully determined using the SPE-LC-MS/MS (MRM) technique (Supporting Information Figure S2). Identification

FIGURE 3. Detection of NDMA, NPip, NPyr, and NDPhA in a treated drinking water sample collected from location 3. and quantification of the individual compounds was achieved using the MRM monitoring of characteristic ions of the target compounds. The SPE method was successfully integrated with the LC-MS/MS detection, enabling ultrasensitive determination of these nitrosamines. Identification of New Nitrosamine DBPs in Drinking Water. The optimized SPE-LC-MS/MS was used to identify nitrosamines in drinking water samples. Both source water and treated water samples from a water treatment plant were analyzed using the SPE-LC-MS/MS (MRM) method. Four of the nine nitrosamines, NDMA, NPyr, NPip, and NDPhA, were detected in the treated water samples but not in the source water samples. The other five nitrosamines were not detected in either the source water or the treated water samples. Figure 3 shows the chromatograms obtained by monitoring the precursor/product ions of m/z 75/43, m/z 101/55, m/z 115/ 69, and m/z 199/169 from the analysis of a treated water sample. Based on the retention times and the mass-to-charge (m/z) ratios of the ions, these peaks were identified as NDMA (m/z 75/43), NPyr (m/z 101/55), NPip (m/z 115/69), and NDPhA (m/z 199/169). The identification of these peaks was initially confirmed by analysis of spiked samples showing the same retention time match of the standards with the target analytes and by product ion mass spectral analysis. NDMA, NPyr, and NPip were also confirmed using the established GC/MS method (16). GC/MS is not able to analyze NDPhA due to thermal decomposition of this compound at the injector. The presence of NDPhA as a consequence of the water disinfection process was confirmed by analyzing pure water blanks, source water, and treated water samples and comparing them with the standard (Figure 4). NDPhA was detected only in the treated water but not in the blanks and the source water. Similar results were also obtained for NDMA, NPyr, and NPip. The results suggest that NDPhA, NDMA, NPyr, and NPip resulted from disinfection processes.

FIGURE 4. Determination of NDPhA in (A) blank, (B) source water, (C) treated water sample collected from the water plant, (D) treated water sample collected from a location in the distribution system, and (E) standard NDPhA. Quantification of Nitrosamines in Water. The key analytical parameters for quantification, including recoveries, method detection limits (MDL), and relative response factors (RRFs) for the nine nitrosamines, are summarized in Table 1. The recoveries of the nine nitrosamines were obtained from triplicate analyses, when spiked samples containing 10 and 40 ng/L (each) of the nine standards in Optima water were separately extracted by SPE and analyzed by LC-MS/ MS. The average recoveries ranged from 65% for NMor to 111% for NDPhA at 40 ng/L and from 41% for NPyr to 96% for NDBA at 10 ng/L. The recovery of NDMA-d6 at spiked concentration as low as 10 ng/L was 63% with a SD of 6%. The MDLs of the nine compounds by the SPE-LC-MS/MS method were 0.1-3.1 ng/L (except 10.6 ng/L for NDEA), obtained from duplicate extractions of samples containing 10 ng/L and triplicate LC-MS/MS analyses of each extract. These results are comparable with those obtained by GC/ MS (16). The excellent method detection limits make the ultratrace analysis of nitrosamines possible. Distribution of Four Nitrosamine DBPs in a Drinking Water Distribution System. Having detected four nitrosamines in the treated water samples, we further investigated the distribution of these nitrosamines in this distribution system. Water samples were collected from the water treatment plant (location 1) and three other locations (2-4) within the same distribution system. Locations 2-4 are numbered in order of increasing distance from the water plant. Being the furthest away from the water plant, location 4 represents the longest residence time in this distribution system. Table 2 shows the concentrations of NDMA, NPyr, VOL. 40, NO. 24, 2006 / ENVIRONMENTAL SCIENCE & TECHNOLOGY

9

7639

TABLE 1. Relative Response Factor (RRF), Recovery, and Method Detection Limit (MDL) of the Nine N-Nitrosamines and the Surrogate Standard NDMA-d6 recoveryb (%) compounds

ion pair (m/z)

RRFa

40 ppt

10 ppt

MDLc (ng/L)

NDMA-d6 81/46 0.23 ( 0.02 77 ( 5 63 ( 6 NA NDMA 75/43 0.17 ( 0.01 78 ( 6 42 ( 10 3.1 NMEA 89/61 0.67 ( 0.04 75 ( 2 77 ( 8 2.4 NPyr 101/55 2.49 ( 0.28 82 ( 7 41 ( 7 2.1 NDEA 103/75 0.39 ( 0.01 93 ( 1 ND 10.6d NPip 115/69 3.5 ( 0.11 105 ( 9 81 ( 3 0.9 NMor 117/87 1.1 ( 0.10 65 ( 7 69 ( 7 0.2 NDPA 131/89 1.61 ( 0.12 82 ( 6 65 ( 6 0.2 NDBA 159/103 0.88 ( 0.07 76 ( 9 96 ( 10 3.1 NDPhA 199/169 4.75 ( 0.28 111 ( 3 56 ( 5 0.1 a

RRF was the average of six values obtained from different concentrations ranging from 5 to 200 µg/L. b Recovery values were the mean of the triplicate analyses of spiked water samples containing either 40 or 10 ng/L. c MDL was obtained from duplicate SPE extractions of water samples containing 10 ng/L nitrosamines and triplicate LCMS/MS analyses of each SPE extracts. NA - not available. d MDL for NDEA was estimated from the analysis of a water sample spiked with 40 ng/L NDEA.

TABLE 2. Concentrations of NDMA, NPyr, NPip, and NDPhA in a Water Distribution Systema concentrations (ng/L) locations 1 2 3 4

NDMA 0 51.7 ( 4.7 65.0 ( 2.7 108.2 ( 11.7

NPyr

NPip

18.0 ( 1.1 33.1 ( 0.3 47.2 ( 1.5 59.8 ( 1.1 43.9 ( 3.2 59.8 ( 5.6 70.5 ( 5.1 117.8 ( 6.2

NDPhA 0 0.65 ( 0.05 1.86 ( 0.13 0.85 ( 0.01

a Location 1 is the water plant, and locations 2-4 are numbered in order of increasing distance from the plant.

NPip, and NDPhA in water samples collected at the four locations. In general, their concentrations increase with increasing distance from the water plant. This is probably because these nitrosamines are produced both during the initial water treatment at the plant and within the distribution system. An appropriate amount of residual disinfectant (e.g., chlorine) is needed in the distribution system to maintain proper water disinfection. Because of the presence of the residual disinfectant and the natural organic matter in the water, disinfection byproducts continue to form in the distribution system. Therefore, the concentrations of the observed nitrosamines increase initially with increasing distance from the water plant. This increase reaches a maximum because both formation and decomposition of DBPs take place. Indeed, the concentration of NDPhA initially increases from locations 1-3 and then decreases when it reaches location 4. The LC-MS/MS (MRM) method provides high sensitivity, specificity, and the capability of detecting both thermally stable and labile nitrosamines, enabling the detection of NDMA, NPyr, NPip, and NDPhA in drinking water. NPip and NDPhA have not been previously reported as DBPs. Our laboratory previously confirmed NDMA in this water system, and we observed NMor and NPyr in the treated water samples at levels close to the limit of detection by the GC/MS method (16). The LC-MS/MS is potentially capable of detecting different DBPs including labile nitrosamines that cannot be detected by GC/MS. The sensitivity and reproducibility of the SPE-LC-MS/MS (MRM) technique is comparable with those of GC/MS for thermally stable nitrosamines. It is useful for future epidemiological and toxicological studies, evalu7640

9

ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 40, NO. 24, 2006

ation of water disinfection processes, and water quality surveillance.

Acknowledgments This study is partially supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canadian Water Network, Alberta Health and Wellness, an NSERC University Faculty Award (to X.F.L.), and an NSERC Undergraduate Summer Research Award and Alberta Heritage Foundation for Medical Research (AHFMR) Summer Research Studentship (to J.B.). The authors would like to thank Dr. Jeffrey W. A. Charrois (Alberta Research Council) for his technical support and constructive discussions.

Supporting Information Available Table containing the optimized LC-MS/MS (MRM) conditions for analysis of nine nitrosamines and two figures showing their structures and chromatograms. This material is available free of charge via the Internet at http:// pubs.acs.org.

Literature Cited (1) Akin, E. W.; Hoff, J. C.; Lippy, E. C. Waterborne outbreak control: which disinfectant? Environ. Health Perspect. 1982, 46, 7-12. (2) Richardson, S. D. Drinking Water Disinfection By-products. In The Encyclopedia of Environmental Analysis and Remediation; Meyers, R. A., Ed.; Wiley: New York, U.S.A., 1998; p 1398. (3) Richardson, S. D. Disinfection by-products and other emerging contaminants in drinking water. Trends Anal. Chem. 2003, 22 (10), 666-684. (4) Richardson, S. D.; Ellington, J. J.; Crumley, F. G.; Evans, J. J.; Plewa, M. J.; Wagner, E. D.; McKague, A. B. Occurrence of iodoacid DBPs in U.S. chloraminated drinking waters. Prepr. Ext. Abstr. ACS Natl. Meet. Am. Chem. Soc. Div. Environ. Chem. 2006, 46 (1), 542-546. (5) Plewa, M. J.; Wagner, E. D.; Richardson, S. D.; Thruston, A. D., Jr.; Woo, Y.; McKague, A. B. Chemical and biological characterization of newly discovered iodoacid drinking water disinfection byproducts. Environ. Sci. Technol. 2004, 38 (18), 47134722. (6) Plewa, M. J.; Wagner, E. D.; Jazwierska, P.; Richardson, S. D.; Chen, P. H.; McKague, A. B. Halonitromethane drinking water disinfection byproducts: chemical characterization and mammalian cell cytotoxicity and genotoxicity. Environ. Sci. Technol. 2004, 38 (1), 62-68. (7) Integrated Risk Information System. United States Environmental Protection Agency (EPA), Office of Research and Development (ORD). http://www.epa.gov/subst/0045.htm (accessed month, year). (8) Taguchi, V. Y.; Jenkins, S. W. D.; Wang, D. T.; Palmentier, J. F. P.; Reiner, E. J. Determination of N-nitrosodimethylamine by isotope dilution, high-resolution mass spectrometry. Can. J. Appl. Spectrosc. 1994, 39 (3), 87-93. (9) California Department of Health Services. California Drinking Water: Activities Related to NDMA and other Nitrosamines. http://www.dhs.ca.gov/ps/ddwem/chemicals/NDMA/NDMAindex.htm (accessed month, year). (10) Government of Ontario. Safe Drinking Water Act 2002. Ontario Regulation 169/03, Schedule 2. http://www.ene.gov.on.ca/envision/water/sdwa/legislation.htm (accessed month, year). (11) Andrzejewski, P.; Kasprzyk-Hordern, B.; Nawrocki, J. The hazard of N-nitrosodimethylamine (NDMA) formation during water disinfection with strong oxidants. Desalination 2005, 176 (13), 37-45. (12) US EPA. Unregulated Contaminant Monitoring Regulation (UCMR) for public water systems revisions. Fed. Regist. 70 (161). August 22, 2005. (13) Mitch, W. A.; Sharp, J. O.; Trussell, R. R.; Valentine, R. L.; AlvarezCohen, L.; Sedlak, D. L. N-Nitrosodimethylamine (NDMA) as a drinking water contaminant: A review. Environ. Eng. Sci. 2003, 20 (5), 389-404. (14) Najm, I.; Rhodes Trussell, R. NDMA formation in water and wastewater. J. Am. Water Works Assoc. 2001, 93 (2), 92-99. (15) Poole, C. F. New trends in solid-phase extraction. Trends Anal. Chem. 2003, 22 (6), 362-373. (16) Charrois, J. W. A.; Arend, M. W.; Froese, K. L.; Hrudey, S. E. Detecting N-nitrosamines in drinking water at nanogram per

(17)

(18) (19) (20) (21)

(22) (23)

(24)

(25) (26) (27)

(28)

(29)

liter levels using ammonia positive chemical ionization. Environ. Sci. Technol. 2004, 38 (18), 4835-4841. Richardson, S. D.; Thruston, A. D., Jr.; Caughran, T. V.; Chen, P. H.; Collette, T. W.; Schenck, K. M.; Lykins, B. W., Jr.; RavAcha, C.; Glezer, V. Identification of new drinking water disinfection by-products from ozone, chlorine dioxide, chloramine, and chlorine. Water, Air, Soil Pollut. 2000, 123 (1-4), 95102. Richardson, S. D. Environmental mass spectrometry: emerging contaminants and current issues. Anal. Chem. 2004, 76 (12), 3337-3364. Richardson, S. D. The role of GC-MS and LC-MS in the discovery of drinking water disinfection by-products. J. Environ. Monit. 2002, 4 (1), 1-9. Richardson, S. D.; Ternes, T. A. Water analysis: emerging contaminants and current issues. Anal. Chem. 2005, 77 (12), 3807-3838. Jenkins, S. W. D.; Koester, C. J.; Taguchi, V. Y.; Wang, D. T.; Palmentier, J. F. P.; Hiong, K. P. N-Nitrosodimethylamine determination in drinking water using a rapid, solid-phase extraction method. Environ. Sci. Pollut. Res. Int. 1995, 2 (4), 207-210. Raksit, A.; Johri, S. Determination of N-nitrosodimethylamine in environmental aqueous samples by isotope-dilution GC/ MS-SIM. J. AOAC Int. 2001, 84 (5), 1413-1419. Mitch, W. A.; Sedlak, D. L. Characterization and fate of N-nitrosodimethylamine precursors in municipal wastewater treatment plants. Environ. Sci. Technol. 2004, 38 (5), 14451454. Wilczak, A.; Assadi-Rad, A.; Lai, H. H.; Hoover, L. L.; Smith, J. F.; Berger, R.; Rodigari, F.; Beland, J. W.; Lazzelle, L. J.; Kincannon, E. G.; Baker, H.; Heaney, C. T. Formation of NDMA in chloraminated water coagulated with DADMAC cationic polymer. J. Am. Water Works Assoc. 2003, 95 (9), 94-106. Ikeda, K.; Migliorese, K. G. Analysis of nitrosamines in cosmetics. J. Soc. Cosmet. Chem. 1990, 41 (5), 283-333. Cheng, R. C. Alternative methods for the analysis of NDMA and other nitrosamines in water and wastewater; Report WRF-01001; WaterReuse Foundation: 2006. Environmental Protection Agency (EPA521). Determination of Nitrosamines in Drinking Water by Solid-Phase Extraction and Capillary Column Gas Chromatography with Large Volume Injection and Chemical Ionization Tandem Mass Spectrometry. http://www.epa.gov/nerlcwww/ordmeth.htm (accessed month, year). Wang, Z.; Xu, H.; Fu, C. Sensitive fluorescence detection of some nitrosamines by precolumn derivatization with dansyl chloride and high-performance liquid chromatography. J. Chromatogr. 1992, 589 (1-2), 349-352. Fu, C.; Xu, H.; Wang, Z. Sensitive assay system for nitrosamines utilizing high-performance liquid chromatography with per-

oxyoxalate chemiluminescence detection. J. Chromatogr. 1993, 634 (2), 221-227. (30) Cardenes, L.; Ayala, J. H.; Gonzalez, V.; Afonso, A. M. Fast microwave-assisted dansylation of N-nitrosamines. Analysis by high-performance liquid chromatography with fluorescence detection. J. Chromatogr., A 2002, 946 (1-2), 133-140. (31) Perez-Ruiz, T.; Martinez-Lozano, C.; Tomas, V.; Martin, J. Flow injection chemiluminescent determination of N-nitrosodimethylamine using photogenerated tris(2,2′-bipyridyl)ruthenium(III). Anal. Chim. Acta 2005, 541 (1-2), 69-74. (32) Perez-Ruiz, T.; Martinez-Lozano, C.; Tomas, V.; Martin, J. Automated solid-phase extraction and high-performance liquid chromatographic determination of nitrosamines using postcolumn photolysis and tris(2,2′-bipyridyl)ruthenium(III) chemiluminescence. J. Chromatogr., A 2005, 1077 (1), 49-56. (33) Filho Pedro, J. S.; Rios, A.; Valcarcel, M.; Caramao, E. B. Development of a new method for the determination of nitrosamines by micellar electrokinetic capillary chromatography. Water Res. 2003, 37 (16), 3837-3842. (34) Sanches Filho, P. J.; Rios, A.; Valcarcel, M.; Zanin, K. D.; Caramao, E. B. Determination of nitrosamines in preserved sausages by solid-phase extraction-micellar electrokinetic chromatography. J. Chromatogr., A 2003, 985 (1-2), 503-512. (35) Li, C. C.; Chen, Z.; Wen, D. W.; Zhang, J. X.; Cong, W. H.; Yu, B.; Liao, Y. P.; Liu, H. W. Determination of tobacco-specific N-nitrosamines in rabbit serum by capillary zone electrophoresis and capillary electrophoresis-electrospray ionization-mass spectrometry with solid-phase extraction. Electrophoresis 2006, 27 (11), 2152-2163. (36) Wagner, K. A.; Finkel, N. H.; Fossett, J. E.; Gillman, I. G. Development of a quantitative method for the analysis of tobacco-specific nitrosamines in mainstream cigarette smoke using isotope dilution liquid chromatography/electrospray ionization tandem mass spectrometry. Anal. Chem. 2005, 77 (4), 1001-1006. (37) Xia, Y.; McGuffey, J. E.; Bhattacharyya, S.; Sellergren, B.; Yimaz, E.; Wang, L. Q.; Bernert, J. T. Analysis of the tobacco-specific nitrosamine 4-(methyinitrosamino)-1-(3-pyridyl)-1-butanol in urine by extraction on a molecularly imprinted polymer column and liquid chromatography/atmospheric pressure ionization tandem mass spectrometry. Anal. Chem. 2005, 77 (23), 76397645.

Received for review June 2, 2006. Revised manuscript received September 28, 2006. Accepted September 28, 2006. ES061332S

VOL. 40, NO. 24, 2006 / ENVIRONMENTAL SCIENCE & TECHNOLOGY

9

7641