Environmental Mass Spectrometry: Emerging ... - ACS Publications

Anal. Chem. 2010, 82, 4742–4774

Environmental Mass Spectrometry: Emerging Contaminants and Current Issues Susan D. Richardson National Exposure Research Laboratory, U.S. Environmental Protection Agency, Athens, Georgia 30605 Review Contents Background Major Analysis Trends Sampling and Extraction Trends Chromatography Trends Online Analysis Emerging Contaminants The New Contaminant Candidate List-3 (CCL-3) General Reviews Sucralose and Other Artificial Sweeteners Antimony Nanomaterials PFOA, PFOS, and Other Perfluorinated Compounds Pharmaceuticals, Hormones, and Endocrine Disrupting Compounds Pharmaceuticals Review Articles New Analytical Methods Occurrence of Illicit Drugs Occurrence in Biological Samples Source to Tap Other Occurrence Studies Fate Studies Endocrine Disrupting Compounds and Hormones Hormones Other EDCs Drinking Water and Swimming Pool Disinfection Byproducts Drinking Water DBPs Combining Chemistry with Toxicology New Methods Near Real-Time Methods Occurrence Studies Biological Measurements Nitrosamines DBPs of Pollutants New Swimming Pool Research Sunscreens/UV Filters Brominated Flame Retardants Benzotriazoles Dioxane Siloxanes Naphthenic Acids Musks Pesticide Transformation Products and New Pesticides Perchlorate Algal Toxins Microorganisms Contaminants on the Horizon: Melamine-Cyanuric Acid Melamine-Cyanuric Acid Literature Cited

4742 4742 4743 4743 4744 4744 4744 4744 4746 4747 4747 4748 4751 4751 4751 4752 4753 4753 4754 4754 4755 4756 4756 4757 4757 4757 4758 4759 4759 4760 4760 4760 4762 4762 4762 4763 4765 4765 4765 4766 4766 4767 4768 4769 4770 4770 4770 4771

BACKGROUND This biennial review covers developments in environmental mass spectrometry for emerging environmental contaminants over the period of 2008 to 2009. A few significant references that 4742

Analytical Chemistry, Vol. 82, No. 12, June 15, 2010

appeared between January and February 2010 are also included. Analytical Chemistry’s current policy is to limit reviews to a maximum of 250 significant references and to mainly focus on new trends. Even with a more narrow focus, only a small fraction of the quality research publications could be discussed. This was especially true this year with the continued explosive growth in the pharmaceutical area, where my entire allotment of 250 references could have been used in this one section alone. As a result, as with the previous review on environmental mass spectrometry in 2008 (1), this review will not be comprehensive but will highlight new areas and discuss representative papers in the areas of focus. I write a similar review article on water analysis, which also focuses on emerging contaminants (2). That review article is somewhat different from this one, in that it focuses only on water contaminants and includes additional analytical methods beyond mass spectrometry. This review on environmental mass spectrometry focuses on methods and occurrence/fate studies utilizing mass spectrometry but also includes the study of air, soil/ sediment, and biological samples, in addition to water. I welcome any comments you have on this review ([email protected]). Numerous abstracts were consulted before choosing the best representative ones to present here. Abstract searches were carried out using Web of Science, and in many cases, full articles were obtained. A table of acronyms is provided (Table 1) as a quick reference to the acronyms of analytical techniques and other terms discussed in this review. Major Analysis Trends. One of the hottest trends over the last 2 years has been the use of liquid chromatography (LC) with high resolution mass spectrometry (MS) to identify unknown contaminants (often degradation or reaction products of the parent contaminant) or to provide further selectivity for known analytes. Full scan and high resolution mass spectrometry have been used with gas chromatography (GC) in a similar fashion for decades, enabling the identification of many environmental contaminants. With recent instrumental development for LC/mass spectrometers, especially time-of-flight (TOF), this full scan and high resolution/accurate mass benefit is now being utilized both for target analytes and also for identifying nontarget analytes that are highly polar or nonvolatile or have a high molecular weight and are not amenable to GC. As a result, within a single analytical run, both target and nontarget analytes can be analyzed or identified. In comparison to triple quadrupole mass spectrometers, which operate at unit resolution and generally in the selected reaction monitoring (SRM) or multiple reaction monitoring (MRM) modes for specific target analytes, TOF-mass spectrometers are capable of acquiring full-scan mass spectra at high 10.1021/ac101102d Not subject to U.S. Copyright. Publ. 2010 Am. Chem. Soc. Published on Web 05/25/2010

Table 1. List of Acronyms APCI APPI BP-3 BSTFA CCL DBPs E1 E2 E3 EE2 ECD EDCs EI ELISA EPA ESA ESI FAIMS FT FTOHs GC HAAs HILIC IC ICM ICP IDA LC MALDI 4-MBC MCL MDL MIMS MRM MS MX NCI NDEA NDMA NMEA NMor NMR NOM OC ODPABA PCBs PBDEs PFCs PFCAs PFDA PFHxA PFHpA PFHS PFNA PFOA PFOS PFOSA PFUnDA REACH SPE SPME THMs TOF UCMR-2 UPLC

atmospheric pressure chemical ionization atmospheric pressure photoionization benzophenone-3 bis(trimethylsilyl)trifluoroacetamide Contaminant Candidate List disinfection byproducts estrone 17β-estradiol estriol 17R-ethinylestradiol electron capture detection endocrine disrupting compounds electron ionization enzyme-linked immunosorbent assay Environmental Protection Agency ethane sulfonic acid electrospray ionization high-field asymmetric waveform ion mobility spectrometry Fourier-transform fluorinated telomer alcohols gas chromatography haloacetic acids hydrophilic interaction chromatography ion chromatography iodinated X-ray contrast media inductively coupled plasma information dependent aquisition liquid chromatography matrix-assisted laser desorption ionization 4-methylbenzylidene camphor maximum contaminant level method detection limit membrane introduction mass spectrometry multiple reaction monitoring mass spectrometry 3-chloro-(4-dichloromethyl)-5-hydroxy-2(5H)-furanone negative chemical ionization N-nitrosodiethylamine nitrosodimethylamine N-nitrosomethylethylamine N-nitrosomorpholine nuclear magnetic resonance natural organic matter octocrylene octyl-dimethyl-p-aminobenzoic acid polychlorinated biphenyls polybrominated diphenyl ethers perfluorinated compounds perfluorocarboxylic acids perfluorodecanoic acid perfluorohexanoic acid perfluoroheptanoic acid perfluorohexanesulfonate perfluorononanoic acid perfluorooctanoic acid perfluorooctane sulfonate perfluorooctane sulfonamide perfluoroundecanoic acid Registration, Evaluation, and Authorization of Chemicals solid-phase extraction solid-phase microextraction trihalomethanes time-of-flight the second Unregulated Contaminants Monitoring Rule ultraperformance liquid chromatography

resolution for all analytes without loss in sensitivity. Because most TOF mass spectrometers have a resolution of at least 10 000 at full-width-half-maximum (fwhm) peak height, isotopic patterns are evident and empirical formulas and chemical structures can be proposed for unknowns or confirmed for target analytes. This also makes it possible to use mass spectral libraries and enable the data file to be reinterrogated months later to find additional unknown contaminants. In addition to TOF-mass spectrometers, linear ion trap-Fourier transform (FT)-Orbitrap mass spectrom-

eters are also now being used for similar high resolution-full scan applications. Researchers are also increasingly using isotopically labeled standards (deuterated or 13C-labeled) to allow more accurate quantitation in a variety of sample matrixes (especially for wastewater samples, where matrix effects and ion suppression can be substantial). Atmospheric pressure photoionization (APPI) is also increasingly being used with LC/MS because it provides improved ionization for more nonpolar compounds, such as nanomaterials (e.g., fullerenes), hormones, UV filters, and polybrominated diphenyl ethers (PBDEs). Sampling and Extraction Trends. The use of molecularly imprinted polymers (MIPs) for selective extraction of environmental contaminants has continued to grow the last 2 years. MIPs are synthetic polymers made with specific recognition sites that are complementary in shape, size, and functional group to the analyte of interest. The recognition sites mimic the binding sites of antibodies and enzymes. Because they are highly specific to the target analytes of interest, MIPs can be used to extract and isolate them from other matrix components in a complex mixture. MIPs have now been synthesized for a number of emerging contaminants, including pharmaceuticals, pesticides, pesticide metabolites, endocrine disrupting compounds (EDCs), and algal toxins. Solid-phase extraction (SPE) cartridges remain the most popular means of extraction and concentration for most emerging contaminants, but this area continues to change also, as new sorbents are manufactured that offer improved recoveries for polar analytes and dual-phase media are being used to capture a broader range of analytes within a single extraction. Solventless extraction techniques, such as solid-phase microextraction (SPME), singledrop microextraction (SDME), stir bar sorptive extraction, and hollow-fiber membrane microextraction, also continue to be used in many applications. Polar organic chemical integrative samplers (POCIS) are also popular. These POCIS extraction devices have membranes that allow polar contaminants to be passively extracted from water and wastewater. Chromatography Trends. The fastest growing chromatography trend continues to be the use of ultraperformance liquid chromatography (UPLC). UPLC is a recently developed LC technique that uses small diameter particles (typically 1.7 µm) in the stationary phase and short columns, which allow higher pressures and, ultimately, narrower LC peaks (5-10 s wide). In addition to providing narrow peaks and improved chromatographic separations, UPLC dramatically shortens analysis times, often to 10 min or less. Other significant chromatography trends include the use of two-dimensional GC (GC × GC) and hydrophilic interaction chromatography (HILIC). GC × GC enables enhanced separations of complex mixtures through greater chromatographic peak capacity and allows homologous series of compounds to be easily identified. It also enables the detection of trace contaminants that would not have been identified through traditional GC. TOFMS is often used as the detector for GC × GC because of its rapid acquisition capability. HILIC is a relatively new LC technique that provides improved separations and detection for highly polar compounds. The stationary phase in HILIC columns has a polar end group (such as an amino group), and retention is based on the affinity of the polar analyte for the charged end group of the Analytical Chemistry, Vol. 82, No. 12, June 15, 2010

4743

column stationary phase. Examples of the use of HILIC in this review include the measurement of haloacetic acids in drinking water and the analysis of melamine-cyanuric acid complexes. Online Analysis. Online SPE coupled to LC/MS/MS is being increasingly used, as it provides high sensitivity and selectivity, minimum sample preparation, more reproducibility, and automation. Examples of new online SPE-LC/MS/MS methods discussed in this review can be seen in the sections on Sucralose and Other Artificial Sweeteners and Pharmaceuticals, Hormones, and Endocrine Disrupting Compounds. Emerging Contaminants. Five new classes of emerging contaminants are added to this Environmental Mass Spectrometry Review this year: sucralose (and other artificial sweeteners), antimony, siloxanes, musks, and melamine-cyanuric acid. Sucralose (also known as Splenda or SucraPlus) is a relatively new artificial sweetener that is now being found in environmental waters (in rivers, lakes, groundwaters, and seawater) and is recognized as persistent. In addition, two new studies from 2009 report on the occurrence and persistence of other artificial sweeteners, including acesulfame, saccharin, and cyclamate, as well as sucralose. Antimony is a well-known, historical contaminant, but new research shows that it can also be a contaminant in bottled water, leaching from polyethylene terephthalate (PET) plastic bottles, where it is used as a catalyst in the production of these plastics. Siloxanes are widely used in consumer products, such as cosmetics, deodorants, soaps, hair conditioners, hair dyes, car waxes, baby pacifiers, cookware, cleaners, furniture polishes, and water-repellent windshield coatings, and researchers are now finding them in environmental waters. Synthetic musks are widely used fragrance additives in perfumes, lotions, sunscreens, deodorants, and laundry detergents and are now known to be widespread in the environment and to accumulate in wildlife and humans. Melamine, and more specifically, melamine-cyanuric acid, became an important contaminant in 2007, after it was discovered to have been deliberately added to wheat gluten products from China, which made their way into petfoods and infant formula, causing illness and death in numerous pets (especially cats) in the U.S. and Canada and illness and death in infants in China. Many new methods have been developed over the last 2 years to measure melamine and melamine-cyanuric acid, and occurrence studies in food products have also been conducted. Other areas covered in this review again include nanomaterials, perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and other perfluorinated compounds (PFCs), pharmaceuticals, hormones, EDCs, drinking water disinfection byproducts (DBPs), sunscreens/UV filters, brominated flame retardants (including polybrominated diphenyl ethers), benzotriazoles, naphthenic acids, algal toxins, perchlorate, dioxane, pesticide degradation products, and microorganisms. These continue to be intense areas of research. An ongoing trend in research for most of these emerging contaminants continues to be investigating ways to remove them from environmental waters (e.g., through reverse osmosis, microfiltration, advanced oxidation, photolysis, microbial degradation, etc.). Because researchers often find that the contaminants are not completely removed with these technologies, the identification of intermediates and degradation products becomes important, as well as the toxicity evaluation of the treated waters to determine whether the treatment significantly reduced the 4744


toxicity. In this regard, there are many more researchers who are combining analytical chemistry with toxicology. The New Contaminant Candidate List-3 (CCL-3). In September 2009, the U.S. Environmental Protection Agency (EPA) published the final CCL-3, which is a drinking water priority contaminant list for regulatory decision making and information collection. The listed contaminants are known to occur or anticipated to occur in drinking water systems and will be considered for potential regulation. This final CCL-3 contains 104 chemicals and 12 microbial contaminants (Table 2) and is somewhat different from the original proposed CCL-3 in 2008. This final CCL-3 now includes PFOA and PFOS, three pharmaceuticals (erythromycin, R-ethinylestradiol [EE2], and nitroglycerin), eight hormones (17R-estradiol, 17β-estradiol, equilenin, equilin, estriol, estrone, mestranol, and norethindrone), and several DBPs (chlorate, formaldehyde, acetaldehyde, and five nitrosamines), as well as pesticides, pesticide degradation products, metals, industrial solvents/ingredients, and specific algal toxins (microcystin-LR, anatoxin-a, and cylindrospermopsin). GENERAL REVIEWS This section includes general reviews relating to environmental mass spectrometry and emerging contaminants. Reviews that relate to specific areas (e.g., PFCs, pharmaceuticals, DBPs) can be found in those specific sections. Many reviews have been published over the last 2 years that relate to environmental mass spectrometry, and a few focus specifically on emerging contaminants. My other biennial review on water analysis published in 2009 discussed advances in research for emerging contaminants including sucralose, antimony, nanomaterials, PFCs, pharmaceuticals, hormones, EDCs, drinking water and swimming pool DBPs, sunscreens/UV filters, brominated flame retardants, benzotriazoles, dioxane, siloxanes, naphthenic acids, musks, pesticide degradation products, new pesticides, perchlorate, algal toxins, microorganisms, and melamine-cyanuric acid (2). Also included in this review were new regulations and regulatory methods pertaining to water. Rubio and Perez-Bendito published an excellent review on recent advances in environmental analysis, including discussions of sampling and sample preparation techniques, separation and detection techniques, calibration, and environmetrics (data analysis) (3). Two reviews focused on the use of UPLC/MS for environmental contaminants. Ibanez et al. highlighted the potential of UPLC coupled to TOF-MS for screening organic pollutants in water, emphasizing pharmaceutical and pesticide applications and outlining the use of accurate mass measurements for detecting both target and nontarget analytes (4). In addition, the authors discuss the creation of user libraries to facilitate future detections of contaminants. Guillarme et al. reviewed the use of UPLC/MS for analyzing food and environmental samples, as well as biological fluids and plant extracts (5). Applications to metabolomics were also included. Accurate mass screening and the identification of emerging contaminants with LC-Orbitrap-MS was the focus of another review by Hogenboom et al. (6). Applications for pharmaceuticals, illicit drugs, benzotriazoles, and the identification of unknown contaminants were presented. Several other reviews have focused on emerging contaminants. Giger wrote an excellent overview of advanced analytical methods

Table 2. Final Contaminant Candidate List-3 (CCL-3) chemical contaminants 1,1,1,2-tetrachloroethane 1,1-dichloroethane 1,2,3-trichloropropane 1,3-butadiene 1,3-dinitrobenzene 1,4-dioxane 17R-estradiol 1-butanol 2-methoxyethanol 2-propen-1-ol 3-hydroxycarbofuran 4,4′-methylenedianiline acephate acetaldehyde acetamide acetochlor acetochlor ethanesulfonic acid (ESA) acetochlor oxanilic acid (OA) acrolein alachlor ethanesulfonic acid (ESA) alachlor oxanilic acid (OA) R-hexachlorocyclohexane aniline bensulide benzyl chloride butylated hydroxyanisole captan chlorate chloromethane (methyl chloride) clethodim cobalt cumene hydroperoxide cyanotoxins (anatoxin-a, microcystin-LR, and cylindrospermopsin) dicrotophos dimethipin dimethoate disulfoton diuron equilenin equilin erythromycin 17β-estradiol estriol estrone 17R-ethinylestradiol (EE2) ethoprop ethylene glycol ethylene oxide ethylene thiourea fenamiphos formaldehyde germanium

halon 1011 (bromochloromethane) HCFC-22 hexane hydrazine mestranol methamidophos methanol methyl bromide (bromomethane) methyl tert-butyl ether metolachlor metolachlor ethanesulfonic acid (ESA) metolachlor oxanilic acid (OA) molinate molybdenum nitrobenzene nitroglycerin N-methyl-2-pyrrolidone N-nitrosodiethylamine (NDEA) N-nitrosodimethylamine (NDMA) N-nitroso-di-n-propylamine (NDPA) N-nitrosodiphenylamine N-nitrosopyrrolidine (NPYR) norethindrone (19-norethisterone) n-propylbenzene o-toluidine oxirane, methyloxydemeton-methyl oxyfluorfen perchlorate perfluorooctane sulfonic acid (PFOS) perfluorooctanoic acid (PFOA) permethrin profenofos quinoline RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) sec-butylbenzene strontium tebuconazole tebufenozide tellurium terbufos terbufos sulfone thiodicarb thiophanate-methyl toluene diisocyanate tribufos triethylamine triphenyltin hydroxide (TPTH) urethane vanadium vinclozolin ziram

microbial contaminants Adenovirus Caliciviruses Campylobacter jejuni Enterovirus Escherichia coli (0157) Helicobacter pylori

for measuring hydrophilic and amphiphilic water contaminants (7). In this article, he mentions new developments, including online SPE-LC, large-volume injection, UPLC, high resolution-TOFMS, two-dimensional LC/MS, and two-dimensional GC/MS (GC × GC/TOF-MS), as well as new mass spectrometry developments, including linear ion traps and the Orbitrap. Also included are highly descriptive polarity-volatility diagrams that provide nice visual representations linking specific groups of contaminants with

Hepatitis A virus Legionella pneumophila Mycobacterium avium Naegleria fowleri Salmonella enterica Shigella sonnei

key processes that determine their fate in the environment and give application ranges of GC and LC. Several important groups of emerging contaminants are also mentioned, including surfactants and their metabolites, EDCs, perfluorinated compounds, benzotriazoles, complexing agents, pharmaceuticals, iodinated X-ray contrast media (ICM), gasoline additives, DBPs, and algal toxins. Giger also introduces new contaminants to watch for, including a recent discovery of sucralose (artificial sweetener also Analytical Chemistry, Vol. 82, No. 12, June 15, 2010

4745

known as Splenda) in environmental samples as well as nanomaterials that could potentially enter the aquatic environment. The expanding role of LC/MS for analyzing metabolites and degradation products of food contaminants was the focus of another review by Pico´ and Barcelo´ (8). The use of Q-Trap, Q-TOF, and Orbitrap mass spectrometers, as well as metabolomic approaches were discussed. GC advances were reviewed by van Leeuwen and de Boer, who outlined the greater separation of GC × GC and greater specificity of MS/MS detection, TOF-MS, and high resolution-MS for measuring organic pollutants in the aquatic environment (9). Other reviews focused on the analysis of emerging contaminants in air. For example, Xie and Ebinghaus discussed analytical methods used for determining contaminants, such as PFCs, brominated flame retardants, musks, and alkylphenols in air, and included active and passive sampling techniques, as well as mass spectrometry methods (10). Garcia-Jares et al. reviewed analytical methods and recent occurrence studies in indoor air from contaminants that are part of the European Union’s Registration, Evaluation, and Authorization of Chemicals (REACH) system (11). Specifically, PFCs, polybrominated and phosphate flame retardants, phthalates, musk fragrances, pesticides, and organotins were discussed. REACH is a relatively new European Union program that restricts the manufacture and use of listed substances that pose a risk to human health or the environment (http://ec.europa.eu/enterprise/sectors/chemicals/reach/restrictions/ index_en.htm). Several reviews focused on the fate of emerging contaminants in the environment. For example, La Farre´ et al. published a nice review on the fate and ecotoxicology of emerging contaminants and their metabolites and transformation products in the aquatic environment (12). Pharmaceuticals, hormones, perfluorinated compounds, drinking water DBPs, sunscreens/UV filters, benzotriazoles, and naphthenic acids were included, along with a summary of ecotoxicological effects reported for nanomaterials. Snow et al. reviewed the detection, occurrence, and fate of emerging contaminants in agricultural environments, which included discussions of pharmaceuticals, hormones, veterinary antibiotics, antibiotic resistant genes, and prions (13). Matamoros et al. reviewed the advances in determining degradation intermediates for personal care products in the environment (14). Contaminants included stimulants, fragrances, sunscreens, antimicrobials, and insect repellents. Trace organic chemicals in groundwater recharge were the focus of another review by Diaz-Cruz and Barcelo´ (15). This review is very timely, as several countries, including the United States, have stresses on their water sources due to population growth and drought and have to use treated wastewater to recharge groundwater sources. This article includes a discussion of artificial recharge strategies, issues with groundwater contamination, and the fate and removal of contaminants in groundwater. The measurement of chiral persistent organic pollutants (POPs) and their metabolites was reviewed by Eljarrat et al., who included chiral pesticides and flame retardants and a discussion of chiral GC, LC, and capillary electrophoresis (CE) methods that are typically coupled with mass spectrometry (16). The issue of chirality has become important because many environmental 4746


contaminants are chiral, and often, one enantiomer is toxic and/ or selectively biodegraded, while the other is not. While not reviews themselves, two papers have noteworthy general applicability to analyzing emerging contaminants in environmental samples. These papers focused on the use of computer-aided techniques for identifying organic contaminants and transformation products. In the first, Kern et al. combined LC/high resolution-MS with a target list of predicted microbial degradation products to screen for transformation products of 52 pesticides, biocides, and pharmaceuticals in several surface waters from Switzerland (17). Using this procedure, 19 transformation products were identified, including some that are rarely reported. In the second, Rosal et al. detailed the development and interlaboratory verification of LC/MS libraries for identifying environmental contaminants, including pesticides, illicit drugs, and pharmaceuticals (18). When comparing library searching results, the libraries from two manufacturers’ instruments exhibited different ion abundance ratios in their mass spectra, but the NIST search engine match probability was 96% or greater for 64 out of 67 compounds evaluated. SUCRALOSE AND OTHER ARTIFICIAL SWEETENERS Sucralose (also known as Splenda or SucraPlus) is a relatively new artificial sweetener that is now widely used in North American and Europe. It may seem like an odd compound to include as an emerging contaminant, but it is now being found in environmental waters and is extremely persistent (half-life up to several years) (2). It is made by chlorinating sucrose, where three hydroxyl groups are replaced by chlorine atoms. Sucralose is heat stable, which is why it has replaced other artificial sweeteners (such as aspartame) for baking and is now widely used in soft drinks because of its long shelf life. So far, at least six research groups have investigated its occurrence and fate in the environment: the Norwegian Institute for Air Research (2), the Swedish Environmental Research Institute (2), the European Commission’s Joint Research Centre (19), and most recently from researchers at the University of North Carolina-Wilmington (20), the Water Technology Center in Karlsruhe, Germany (21), and the Swiss Federal Research Station in Wa¨denswil, Switzerland (22). In the groundbreaking multicountry study in Europe (19), Loos et al. used a SPE-LC/negative ion-electrospray ionization (ESI)-MS/MS method with isotope dilution to measure sucralose at a detection limit of ∼10 ng/L. One hundred and twenty samples were collected from rivers in 27 European countries, and sucralose was found up to 1 µg/L, predominantly in samples from the United Kingdom, Belgium, The Netherlands, France, Switzerland, Spain, Italy, Norway, and Sweden, with only minor levels (94%. Acesulfame was more persistent during soil aquifer treatment than in conventional wastewater treatment, such that acesulfame was still present in groundwater after a residence time of 1.5 year. In surface waters, acesulfame was the predominant artificial sweetener found, with concentrations exceeding 2 µg/L; saccharin and cyclamate were found at levels between 50 and 150 ng/L, and sucralose was at 60 to 80 ng/L, with one sample exceeding 100 ng/L. Finally Buerge et al. developed an online-SPE-LC/MS/MS method to measure four artificial sweeteners (sucralose, acesulfame, saccharin, and cyclamate) in environmental waters (22). All four artificial sweeteners were found in most samples analyzed, with acesulfame detected at the highest levels. Acesulfame was consistently detected in untreated and treated wastewater (12-46 µg/L), in most surfaces waters, in 65% of the groundwater samples investigated (up to 4.7 µg/L), and even in several tap water samples (up to 2.6 µg/L) in Switzerland. Because of it recalcitrance to transformation, acesulfame was viewed as an ideal marker for the detection of domestic wastewater in environmental waters, particularly groundwater. Using acesulfame as a chemical marker, the percent contribution of domestic wastewater to environmental waters could be determined. For example, acesulfame levels were used to estimate a ∼10-20% contribution from domestic wastewater to groundwater in the lower Glatt valley in Switzerland. This method is sensitive enough to detect as low as a 0.05% contribution. ANTIMONY Antimony, which can have both acute and chronic toxicity effects, is regulated in drinking water in the United States, Canada, Europe, and Japan at action levels ranging from 2 to 6 µg/L. Antimony contamination can result from copper or lead smelting or from petroleum refineries, but new studies have shown that it can also leach from polyethylene terephthalate (PET) plastic water bottles. Antimony trioxide is used as a catalyst in the manufacture of PET plastics, which can contain >100 mg/kg of antimony. Bottled waters from the United States were the focus of a new study by Westerhoff et al., who used inductively coupled plasma (ICP)-MS to investigate the leaching of antimony in bottled waters upon storage at elevated temperatures (23). The southwestern U.S. was chosen for this study because of its high consumption

of bottled water (hot, desert climate) and elevated temperatures, which could increase antimony leaching from the bottles. Antimony levels ranged from 0.095 to 0.521 µg/L in the bottled water initially (below the U.S. EPA maximum contaminant level (MCL) of 6.0 µg/L), but at higher storage temperatures (similar to summertime temperatures found inside cars, garages, and enclosed storage areas), levels could increase and exceed the MCL. For exposure temperatures of 60, 65, 70, 75, 80, and 85 °C, the time required to exceed the MCL was 176, 38, 12, 4.7, 2.3, and 1.3 days, respectively. In another recent study, Keresztes et al. used ICP-MS to measure antimony leaching from PET bottles into carbonated (sparkling) and noncarbonated (still) mineral waters purchased in Europe (24). Storage conditions (time, temperature, exposure to light) were also investigated. In general, antimony levels were higher in the carbonated waters, and levels exceeded 2 µg/L under extreme light and temperature storage conditions (60-70 °C, 23 W daylight lamp for 116 h). Antimony leaching varied over an order of magnitude among the waters investigated. NANOMATERIALS There is currently a research boom in the area of nanomaterials, with many companies and universities expanding their efforts. New university departments are being developed around the study of nanomaterials, and government investment in nanotechnology has dramatically increased in the last 8 to 9 years. Most research is centered on developing new uses for nanomaterials and new products with unique properties, but on the other side of this, there is also significant concern regarding nanomaterials as environmental contaminants. As such, nanomaterials are the focus of a recent initiative at the U.S. EPA, under which research on nanomaterial fate, transport, and health effects is being conducted. Nanomaterials are 1-100 nm in size and can have unique properties, including high strength, thermal stability, low permeability, and high conductivity. In the near future, nanomaterials are projected to be used in areas such as chemotherapy, drug delivery, and labeling of food pathogens (“nanobarcodes”). The chemical structures of nanomaterials are highly varied, including fullerenes, nanotubes, quantum dots, metal oxanes, TiO2 nanoparticles, nanosilver, and zerovalent iron nanoparticles. Most environmental concerns center on the potential human and ecological effects, and most methods use techniques other than mass spectrometry, such as transmission electron microscopy, quartz crystal microbalance, X-ray photon spectroscopy, light scattering, electrophoretic mobility, LC/UV, Raman spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy (25). In addition, most studies are carried out in “clean” systems and not in real environmental systems. Isaacson et al. published a thorough review on the quantitative analysis of fullerene nanomaterials, which included a report on the state-of-the-art analytical methods for quantifying them, analytical challenges to overcome, and how improvements in analytical methodologies will play an essential role in advancing our understanding of fullerene nanomaterial occurrence, transport, and effects (25). In particular, analytical methods need to provide chemically explicit information, such as molecular weight and the number and identity of surface functional groups (which can be achieved with mass spectrometry), and increased availability is needed for well characterized Analytical Chemistry, Vol. 82, No. 12, June 15, 2010

4747

authentic standards, reference materials, and isotopically labeled internal standards. In another review, Tiede et al. provided an overview of analytical techniques for measuring nanomaterials, which included TOF-MS and aerosol TOF-MS among many other non-MS techniques (26). Analytical challenges were also discussed, including extraction challenges, sample preparation artifacts, distinguishing between natural and engineered nanoparticles, and the lack of reference materials. Morawska et al. reviewed instrumental methods for monitoring airborne nanoparticles in indoor and outdoor environments, including aerosol mass spectrometry techniques (27). In one of the few published MS methods for nanomaterials, Isaacson and Bouchard used asymmetric flow field-flow fractionation (AF4), dynamic light scattering, and LC/APPI-MS to determine aggregate size distributions of C60 fullerenes in aqueous systems (28). This is the first method to use AF4 for fractionating a colloidal suspension of aqueous C60, which provided improved particle size characterization. The authors also made a strong case for the use of MS over other detection techniques, due to the unambiguous determination of the mass of C60 in each size fraction. With this method, aqueous C60 aggregates were shown to contain size distributions between 80 and 150 nM (for 58% of the mass), 69 000 people (ages 1.5 to >100 years old), who had been exposed through contaminated drinking water close to a PFC factory (41). Mean serum levels for PFOA were 32.9 ng/ mL, which are 500% higher than previously reported for a representative American population. Serum concentrations for perfluorohexane sulfonate (PFHS) and PFNA were also elevated by 39 and 73% respectively, whereas PFOS levels were similar to those of the U.S. population. In another human serum study, D’eon et al. used LC/MS/MS to measure polyfluoroalkyl phosphoric acid diesters (diPAPs), some of which can metabolize to form PFOA, to assess exposure to polyfluoroalkyl phosphoric acids (PAPs) that are used to grease-proof food contact paper products (42). Serum samples from people in the Midwestern United States, paper fibers, and wastewater treatment plant sludge were measured in this study. Serum samples from 2004 and 2005 contained up to 4.5 µg/L total diPAPs, which were similar to levels observed for C8 to C11 PFCAs. DiPAPs were found in paper fiber extracts (34-2200 ng/g) and in wastewater treatment plant sludge (47-200 ng/g). In another study, Monroy et al. used LC/MS/ MS to measure PFCs in human maternal and umbilical cord blood samples (43). PFOA and PFOS were detected in all serum samples analyzed. PFOS serum levels were significantly Analytical Chemistry, Vol. 82, No. 12, June 15, 2010

4749

higher in second trimester maternal serum than in maternal serum levels at delivery, which were higher than in the umbilical cord blood. PFHxS was also found in maternal and cord blood samples, at mean concentrations of 4.05 and 5.05 ng/mL, respectively. However, there was no association between serum PFCs at any time point and birth weight. PFCs have also been measured in other environmental samples, including drinking water, river waters, air, and food. Quinones and Snyder used SPE and isotope dilution-LC/MS/MS to measure PFCAs and PFSAs in drinking waters and associated surface waters, groundwaters, and wastewaters from six states in the United States (44). Method reporting limits (MRLs) were 1.0 ng/L, except for PFOA, which was 5.0 ng/L, due to instrumental and procedural background levels. PFOS was the only PFC detected in minimally impacted surface waters, with average levels of 2.0 ng/L or lower. Almost all measured PFCs, except for PFUnDa and PFDoA, were detected in wastewater treatment plant effluents and other highly impacted waters. PFOA showed the highest levels, with an average per site ranging from 26 to 120 ng/L. Compound-specific concentrations in finished drinking water samples were comparable to levels in raw source water samples in almost every case, except one utility that used microfiltration and reverse osmosis for wastewater treatment for indirect potable reuse, where levels were below MRLs. In a large European survey of polar persistent contaminants in river waters, Loos et al. reported levels of PFOS, PFOA, PFHxA, PFHpA, PFNA, PFDA, and PFUnA measured by SPE-LC/MS/ MS in more than 100 rivers from 27 countries (45). PFOA reached concentrations of 174 ng/L, and major sources were the Po, Danube, Scheldt, Rhone, and the Wyre Rivers. PFOS reached concentrations of 1371 ng/L, and major sources were the Scheldt, Seine, Krka, Severn, and the Rhine Rivers. Carpet manufacturing plants have been identified as a major source of PFCs in the environment, and the city of Dalton, GA (U.S.) is known as the carpet capital of the world, accounting for approximately 90% of carpets manufactured worldwide. Konwick et al. investigated PFCs around Dalton, GA, specifically, in surface waters near a wastewater land application system, from neighboring streams and ponds, and from a river (Altamaha River) distant from this location (46). LC/negative ion-ESI-MS/MS was used to measure PFCs. Levels of PFCs were high in the river near this land application site, with PFOA occurring at the highest concentrations (up to 1150 ng/L), followed by PFNA, PFOS, perfluorooctane sulfonamide (PFOSA), PFDA, and PFUnDA. Levels were also high in the streams and ponds in Dalton (PFOA up to 299 ng/L; PFOS up to 120 ng/L); PFC levels were much lower in the river distant from this site, with only low nanogram per liter levels observed. PFOS concentrations at two sites in the Conasauga River exceeded the threshold effect levels predicted for birds. Air and water samples were the focus of a study by Loewen et al., who used both GC/MS (with positive ion CI and negative-CI) and LC/MS/MS to measure PFCs in air and lake water samples collected in Western Canada (47). Results suggested that the abundance of FTOHs in air and PFCAs in water supports atmospheric FTOH degradation as a source of PFCAs in mountain lakes. In a study of foods, Ostertag et al. used LC/MS/MS to measure PFCs in several foods commonly consumed by Canadians (48). PFCs were detected in eight of the samples, including 4750


processed meats, preprepared foods, and peppers, with concentrations ranging from 0.48 to 5.01 ng/g. Mean daily PFC exposure estimates ranged from 1.5 to 2.5 ng/kg of body weight. Total PFCAs in cakes and cookies, lunch meats, and green vegetables were the main contributors to dietary exposure. Several fate and transport studies have also been conducted. For example, Wang et al. used chiral-LC/MS/MS and demonstrated that PFOS can metabolize enantioselectively (49). Microsome incubations revealed that the two enantiomers observed metabolize at significantly different rates. Murakami et al. investigated sources of PFCs in groundwater in Tokyo (50). PFOS was more abundant in groundwater than in river waters, wastewaters, and street runoff, indicating that it was likely produced by degradation of precursors. Soil column tests also supported this. Wastewater and surface runoff contributed 54-86% and 16-46%, respectively, of PFCAs to groundwater. In another study, Ahrens et al. investigated the partitioning behavior of PFCs between pore water and sediment in sediment cores taken from Tokyo Bay (51). Short-chain PFCAs (C e 7) were found exclusively in pore water, while long-chain PFCs (C g 11) were found only in sediment. PFSAs, n-ethylperfluoro-1-octanesulfonamidoacetic acid (N-EtFOSAA), and PFOSA seemed to bind more strongly to sediment than PFCAs. Perfluoroalkyl-chain length and functional group were important parameters that influenced the partitioning of PFCs in sediment. Most fate studies of PFCs have involved the examination of individual species; however, it is the polymers of these materials that are most often used in products, and there is controversy over polymer degradation rates in the environment. Washington et al. used GC/CI-MS and LC/MS/MS to investigate the degradation of fluorotelomer polymers in soil (52). Polymers were incubated in soil microcosms and monitored for possible fluorotelomer and PFC degradation. Polymer half-lives of 870-1400 years were estimated for the course-grained polymer and 10-17 years for the more finely grained polymers. Results revealed that fluorotelomer polymer degradation is a significant source of PFOA and other PFCs in the environment. Wang et al. determined biodegradation pathways, metabolites, and metabolite yields for 8-2 FTOH in aerobic soils, using a 14C analog F(CF2)714CF2CH2CH2OH and analyzing with LC/MS/MS (53). Up to 35% of the 14C dosed was irreversibly bound to soils and was only recovered by soil combustion. The average PFOA yield was approximately 25%; the PFHxA yield reached approximately 4%, and the 14CO2 yield was 6.8%. In addition, three new metabolites were identified: the 3OH-7-3 acid [F(CF2)7CHOHCH2COOH], 7-2 FT ketone [F(CF2)7COCH3], and 2H-PFOA [F(CF2)6CFHCOOH]. The formation of 2H-PFOA, PFHxA, and 14CO2 showed that multiple -CF2- groups were removed from the 8-2 FTOH. Equilibrium acid dissociation constants (pKas) are important for understanding and predicting the fate of chemicals in the environment, but until recently, the pKa of PFOA was not available in the literature. Two previous publications suggest pKas of 3.8 and -0.5 (2). Another paper published in 2009 by Cheng et al. used a different approach (with negative ESI-MS) to estimate the pKa of PFOA and PFOS (54). Because the sum of the signal intensities of negative ions of perfluorooctanoate and PFOS solutions from pH 1.0 to 6.0 were independent of

pH, it was inferred that the pKas of PFOA and PFOSA are 90%), while others, such as ecstasy, methamphetamine, nor-LSD, and THC-COOH, were occasionally or not eliminated at all. Drug consumption estimates showed cocaine to be the most abused drug, followed by cannabis, amphetamine, heroin, ecstasy, and methamphetamine, with total annual consumption estimates of 36 tons. Kasprzyk-Hordern et al. also measured illicit drugs and other pharmaceuticals to estimate drug usage in local communities (83). LC/MS/MS measurements of wastewater indicated that the average usage in South Wales (United Kingdom) for cocaine was 0.9 g/day per 1000 people (equivalent to 1 ton per year), and the average usage of amphetamine was 2.5 g/day per 1000 people. Occurrence in Biological Samples. Since the first report by Brooks’ group from Baylor University (Texas) of human pharmaceuticals accumulating in fish in 2005, other research groups have begun to measure pharmaceuticals in fish. For example, Ramirez et al. reported results from a national pilot study in the United States to assess the accumulation of pharmaceuticals and personal care products in fish sampled from five effluentdominated rivers that receive direct discharge from wastewater treatment plants in Chicago, Dallas, Orlando, Phoenix, and West Chester, PA (84). LC/MS/MS was used to measure 24 pharmaceuticals, and GC/MS/MS was used to measure 12 personal care products in fish livers and fillets. Norfluoxetine, sertraline, diphenhydramine, diltiazem, and carbamazepine were found at nanogram per gram levels in fish fillet composites. Fluoxetine and gemfibrozil were found in liver tissues. Sertraline was detected up to 19 and 545 ng/g in fillet and liver tissues, respectively, and trace levels of triclosan were found. In general, more pharmaceuticals were detected at higher concentrations and with greater Analytical Chemistry, Vol. 82, No. 12, June 15, 2010

4753

frequency in liver than in fillets. In addition, those cities with advanced wastewater treatment (Dallas and Orlando) showed lower overall concentrations, fewer compounds detected, and lower frequency of detection. In another study, Schultz et al. used SPE with LC/MS/MS to measure antidepressants in fish, water, and sediment from two effluent-impacted streams in the United States (85). Antidepressants included fluoxetine, norfluoxetine (degradate), sertraline, norsertraline (degradate), paroxetine, citalopram, fluvoxamine, duloxetine, venlafaxine, and bupropion. Eight of the 10 antidepressants were detected in brain tissue from white sucker fish, at levels up to 3 ng/g. Antidepressants were not found at points upstream of the wastewater treatment plants but were frequently found in surface waters, sediment, and fish downstream of the treatment plants. Leiker et al. identified methyl triclosan and new halogenated analogues in fish (carp) from the Las Vegas Bay (Lake Mead) and in surface waters from the Las Vegas Wash using semipermeable membrane devices (SPMDs) and GC/high resolution-MS (86). The data suggested that a portion of the triclosan entering wastewater treatment was not removed and was converted to methyl triclosan (microbially) and halogenated analogues (by reaction with chlorine in wastewater treatment). Levels of methyl triclosan were an order of magnitude higher than previously reported in the literature (mean of 596 µg/kg wet weight), and high levels of triclosan in the Las Vegas Wash were well above levels shown to disrupt thyroid endocrine systems in amphibians. Halogenated analogues were found at lower levels ( 17R-estradiol > E2 > progesterone >17Rdihydroequilin, which was similar for the agricultural, mixed, and suburban used areas. No antibiotics were detected in the 21 streams sampled. Kang and Price measured the occurrence of phytoestrogens in municipal wastewaters and surface waters using LC/MS/MS (117). High levels of enterolactone (581-2111 ng/ L), daidzein (341-1688 ng/L) and enterodiol (60-834 ng/L) were detected in raw sewage, but most phytoestrogens were removed well in wastewater treatment. Daidzein was found in two creeks, ranging from 2 to 33 ng/L and up to 120 ng/L in a pond on a dairy farm. This demonstrated that direct excretions of livestock can be another potential source of phytoestrogen contamination in environmental waters. Finally, Skotnicka-Pitak et al. published an overview of transformation products of EE2 and E2 from biotic and abiotic degradation, along with a list of structures identified to date (118). Biodegradation, ozonation, and oxidation products are presented, along with the application of LC/MS, NMR, and X-ray crystallography that can be used to unambiguously identify them. Other EDCs. Other EDCs actively being investigated include nonylphenol ethoxylate surfactants and plasticizers. Several reviews have been published in the last 2 years on EDCs. For example, Chang et al. reviewed methods of identification, analysis, and removal of EDCs in water (119). In addition to MS methods, biological methods were also included. Lara-Martin et al. published a review detailing techniques for extracting, separating, and determining synthetic surfactants in aqueous samples, along with a discussion of their reactivity and fate in aquatic environments (120). Fro¨mel and Knepper reviewed the use of MS for investigating the biodegradation of surfactants (121). Morales et al. presented an overview of analytical methods used for measuring alkylphenol ethoxylates and their degradation products in liquid and soil samples (122). In one of the new methods reported for EDCs, Bowden et al. used silyl derivatization and GC/MS to enable the measurement of several EDCs in a single analysis (123). Zafra-Gomez developed a new LC/MS method for measuring 14 EDCs in wastewater, including bisphenol A and its chlorinated derivatives (chloro-, dichloro-, trichloro-, and tetrachlorobisphenol A), 3 alkylphenols (4-nonyl, 4-octyl, and 4-(tert-octyl)phenol), and 6 phthalates (dimethyl-, diethyl-, dibutyl-, butylbenzyl-, bis(2-ethylhexyl), and dioctylphthalate) (124). Quantification limits ranged from 12 to 69 ng/L, and this method was used to study EDCs in urban wastewater from Spain.

A couple of nice studies combined analytical measurements with toxicology. For example, Brix et al. measured alkylphenolic compounds and estrogens in a European river basin (in Spain) and determined the estrogenic potential of the water and sediment (125). Analytes were measured using SPE and LC/MS/MS. The calculated estrogenic potential surpassed the expected effect concentration of 1 ng E2/L at several sampling points, such that the waters could pose an estrogenic risk for aquatic organisms. In another study, Fernandez et al. developed a toxicity identification fractionation (TIF) procedure to determine estrogenic compounds in wastewaters and sludge and combined this with GC/ MS and LC/MS measurements of the fractions (126). The recombinant yeast assay was used to measure the estrogenicity. Fractions contained nonylphenol, nonylphenol ethoxylate, nonylphenol diethoxylate, bisphenol A, synthetic and natural hormones, and hormone conjugates. Wastewater treatment removed 52 to 100% of the compounds; bisphenol A was the least removed. Only alkylphenols accumulated in the sludge. Jonkers et al. investigated the occurrence and behavior of several phenolic EDCs in wastewater and surface waters (127). EDCs included parabens, alkylphenolic compounds, phenylphenol, and bisphenol A. SPE and LC/MS/MS were used to sample the influents and effluents of wastewater treatment plants and river waters. Parabens and nonylphenol polyethoxylates were removed well, but in some cases, nonylphenoxy acetic acid or nonylphenols were formed. Water flows and mass flows varied strongly due to several rain events, but higher water flows did not necessarily result in a proportional dilution of the contaminants. Gonzalez et al. measured nonylphenol and nonylphenol ethoxylates in sewage sludge from different conventional treatment processes (128). The most contaminated samples were compost, anaerobically digested sludge, lagoon sludge, and aerobically digested sludge samples, containing up to 962, 669, 319, and 282 mg/kg km of total nonylphenol and nonylphenol ethoxylate levels, respectively. In an interesting human occurrence study, Lopez-Espinosa et al. measured nonylphenol and octylphenol in adipose tissue of women from Southern Spain (129). Samples were homogenized, extracted using hexane and acetonitrile, further extracted using SPE, derivatized with bis(trimethylsilyl)trifluoroacetamide (BSTFA)/trimethylchlorosilane (TMCS), and analyzed by GC/MS. Nonylphenol was detected in 100% (n ) 20) of the samples, and octylphenol was detected in 23.5% of the samples, with median levels of 57 and 4.5 ng/g, respectively. These levels are similar to levels that have been observed in other countries. DRINKING WATER AND SWIMMING POOL DISINFECTION BYPRODUCTS Drinking Water DBPs. Drinking water DBPs are formed by the reaction of disinfectants (chlorine, chloramines, ozone, chlorine dioxide, etc.) with natural organic matter (NOM) and bromide or iodide in source waters. They can also form by the reaction of disinfectants with other organic contaminants, and there is an increasing amount of research in this area. One particularly important discovery in this regard was the formation of high levels of N-nitrosodimethylamine (NDMA) in drinking water that resulted from the reaction of ozone with a fungicide (tolylfluanid) used in Europe. New areas in drinking water DBP research include the study of highly genotoxic or carcinogenic DBPs that have been recently identified, issues with increased formation of Analytical Chemistry, Vol. 82, No. 12, June 15, 2010

4757

many of these with the use of alternative disinfectants (e.g., chloramines and ozone), and routes of exposure besides ingestion. In this regard, there have been several recent studies of DBPs in swimming pools. Other trends include the development of UPLC/ MS/MS methods and the combination of analytical chemistry with toxicology to account for toxicological effects with DBPs measured. In addition, near real-time methods are being developed, which could give drinking water utilities a better understanding and control over DBP levels received by consumers and improve exposure characterizations for epidemiologic studies. Toxicologically important DBPs include brominated, iodinated, and nitrogen-containing DBPs (“N-DBPs”). Brominated DBPs are generally more carcinogenic than their chlorinated analogues, and new research is indicating that iodinated compounds are more toxic than their brominated analogues (1). Brominated and iodinated DBPs form due to the reaction of the disinfectant (such as chlorine) with natural bromide or iodide present in source waters. Coastal cities, where groundwaters and surface waters can be impacted by salt water intrusion, and some inland locations, whose surface waters can be impacted by natural salt deposits from ancient seas or oil-field brines, are examples of locations that can have high bromide and iodide levels. A significant proportion of the U.S. population and several other countries now live in coastal regions that are impacted by bromide and iodide; therefore, exposures to brominated and iodinated DBPs are of growing interest. Early evidence in epidemiologic studies indicates that brominated DBPs may be associated with reproductive and developmental effects, as well as cancer. Brominated and iodinated DBPs of interest include iodo-acids, bromonitromethanes, iodotrihalomethanes (iodo-THMs), brominated forms of MX (3-chloro4-(dichloromethyl)-5-hydroxy-2(5H)-furanone), haloaldehydes, and haloamides. Iodinated DBPs are increased in formation with chloramination, and bromonitromethanes are increased with the use of preozonation. Besides haloamides, other N-DBPs of interest include NDMA and other nitrosamines, which can form with either chloramination or chlorination (if nitrogen-containing coagulants are used in treatment). Five nitrosamines (NDMA, NDEA, N-nitrosodipropylamine, N-nitrosodiphenylamine, and Nnitrosopyrrolidine), as well as formaldehyde (which is a DBP from treatment with ozone, chlorine dioxide, or chlorine), are currently listed on the U.S. EPA’s new Contaminant Candidate List (CCL3) (www.epa.gov/safewater/ccl). Chloramination has become a popular alternative to chlorination for plants that have difficulty meeting the regulations with chlorine, and its use is expected to increasewiththenewStage2Disinfectants(D)/DBPRule(www.epa. gov/safewater/disinfection/stage2). Krasner published a review on the formation and control of emerging DBPs of health concern (130). Emerging DBPs discussed included iodo-THMs, haloaldehydes, halonitromethanes, and nitrosamines. Some emerging DBPs are associated with impaired drinking water supplies (e.g., impacted by treated wastewater, algae, and iodide). Examples of treatment techniques to control their formation are given, including predisinfection with chlorine, chlorine dioxide, or ozone to destroy precursors for NDMA formation and the use of biofiltration to reduce levels of ozone DBPs. Weinberg reviewed modern approaches for analyzing DBPs in drinking water, which included a summary of methods for measuring regulated and emerging DBPs, including iodo4758


THMs, halonitromethanes, nitrosamines, haloacetamides, and halofuranones (131). Combining Chemistry with Toxicology. More studies are combining DBP identification/measurement efforts with toxicology to understand their potential health effects. For example, Richardson et al. quantified iodo-acids for the first time in chloraminated and chlorinated drinking waters (along with iodoTHMs) and investigated these new DBPs for mammalian cell genotoxicity and cytotoxicity (132). Iodoacetic acid has been previously shown to be the most genotoxic of all DBPs studied to date in mammalian cells, and now, the genotoxicity and cytotoxicity of the other four iodo-acid DBPs identified in drinking water (bromoiodoacetic acid, (E)- and (Z)-3-bromo-3-iodopropenoic acid, and (E)-2-iodo-3-methylbutenedioic acid) are presented, along with the toxicity of other synthesized iodo-acids and iodo-THMs. Iodo-THMs have been known to form in drinking water for some time (since the mid-1970s) but had not been previously investigated for toxicity, probably due to the lack of commercial standards. Until recently, only iodoform was commercially available, so the other iodo-THMs had to be synthesized. Of the 13 iodo-DBPs analyzed, 7 were genotoxic, with a rank order of iodoacetic acid . diiodoacetic acid > chlorodiiodomethane > bromoiodoacetic acid > (E)-2-iodo-3-methylbutenedioic acid > (E)3-bromo-3-iodopropenoic acid > (E)-3-bromo-2-iodopropenoic acid. The rank order of cytotoxicity was iodoacetic acid > (E)-3-bromo2-iodopropenoic acid > iodoform > (E)-3-bromo-3-iodopropenoic acid > (Z)-3-bromo-3-iodopropenoic acid > diiodoacetic acid > bromoiodoacetic acid > (E)-2-iodo-3-methylbutenedioic acid > bromodiiodomethane > dibromoiodomethane > bromochloroiodomethane. Liquid-liquid extraction and diazomethane derivatization were used with GC/NCI-MS to quantify the iodo-acids at low nanogram per liter detection limits; SPME with GC/high resolution-EI-MS was used to quantify 2 iodo-THMs (dichloroiodomethane and bromochloroiodomethane) at 2 ng/L detection limits. Iodo-acids were found in finished drinking waters from all of the 23 cities sampled in the U.S. and Canada, up to 1.7 µg/L; iodo-THMs were also found in most finished waters, up to 10.2 µg/L. The use of chloramination clearly increased their formation relative to chlorination, and shorter free chlorine contact times (before ammonia addition to form chloramines) resulted in higher levels of iodo-DBPs. These results supported and expanded on earlier controlled laboratory results of iodoform formation previously conducted in von Gunten’s research group. Results from the first phase of a large integrated study (called the Four Lab Study) involving the collaboration of chemists, toxicologists, engineers, and risk assessors from the four national research laboratories of the U.S. EPA, as well as collaborators from academia and the water industry, was published in a series of papers in a special issue of Journal of Toxicology and Environmental Health. The Four Lab Study aims to understand reproductive and developmental effects, as well as other toxicological effects, that have been observed in humans. The study involved the treatment of natural waters with two disinfection regimes: (1) chlorine and (2) ozone-chlorine. More than 70 priority DBPs were quantified using GC/electron capture detection (ECD) and GC/MS methods, and DBPs were also identified in a comprehensive approach using GC/EI-MS and GC/CI-MS with low and high resolution (133). Several new DBPs were identified in this

effort, including bromodichloropropenoic acids, 2-chloro-3-methylbutanoic acid, iodobutanal, bromo- and iodo-phenols, and bromoalkyltins. Increasingly, ESI-MS/MS is being used to discover new, highly polar DBPs. For example, Qin et al. reported the first haloquinone DBP found in drinking water, 2,6-dichloro-1,4-benzoquinone, using SPE and LC/MS/MS (134). Quantitative structure-toxicity relationship (QSTR) analysis had predicted that haloquinones are highly toxic and may be formed during drinking water treatment. The chronic lowest observed adverse effect levels (LOAELs) of haloquinones are predicted to be in the low microgram per kilogram body weight per day range, which is 1000× lower than most regulated DBPs, except bromate. This new DBP was found in drinking water treated with chlorine and chloramines, as well as chloramines and UV irradiation, at levels ranging from 5.3 to 54.6 ng/L. It has a predicted LOAEL of 49 µg/kg body weight per day. New Methods. Ding and Zhang used UPLC/ESI-MS/MS to provide a more comprehensive picture of polar iodinated DBPs formed in drinking water (135). Precursor scans of iodine (m/z 126.9) allowed iodinated DBPs to be detected in simulated drinking waters treated with chlorine, monochloramine, and chlorine-chloramine. A total of 17 iodo-DBPs were tentatively identified, with chloramination producing the most iodo-DBPs, followed by chlorine-chloramine and then chlorination. Tentatively identified compounds included iodoacetic acid, chloroiodoacetic acid, (E)- and (Z)-iodobutenedioic acid, 4-iodobenzoic acid, 3-iodophthalic acid, 2,4-diiodobenzoic acid, 5,6-diiodosalicylic acid, and 5,6-diiodo-3-ethylsalicylic acid. In addition, two nitrogenous iodo-DBPs were found in chloraminated and chlorine-ammonia treated waters, but the ion abundances were too low to propose structures for them. In another study, Zhang et al. used negative ion-ESI/MS/MS (without LC separation) to allow rapid detection of polar brominated DBPs in drinking water (136). Precursor scans of m/z 79 and 81 revealed the presence of several new brominated DBPs, including 1,1,2-tribromo-1,2,2-tricarboxylethane and 1-bromoamino-1,2-dibromo-1,2,2-tricarboxylethane, which were tentatively identified in chlorinated drinking water. In another paper, Zhai and Zhang developed a new ESI/MS/MS method for differentiating adducts of common drinking water DBPs from higher molecular weight DBPs (137). Finally, Chen et al., developed a new UPLC/negative ion-ESI-MS/MS method to measure 10 haloacetic acids (HAAs) in drinking water, including the 9 commonly measured bromo-chloro-HAAs and iodoacetic acid (138). Detection limits of 1-3 µg/L were achieved; HILIC and BetaMax Acid columns were evaluated. While the HILIC column gave the lowest detection limits, significant matrix effects were observed that could not be corrected for with the internal standard (2-bromobutyric acid). With the BetaMax Acid column, tap water samples could be directly injected and analyzed (but at higher detection limits ranging from 0.18 to 71.5 µg/L). Several other methods have been developed for DBPs. Shi and Adams created a rapid IC/ICP-MS method for simultaneously measuring iodoacetic acids, bromoacetic acids, iodate, bromate, iodide, and bromide (139). Method detection limits ranged from 0.33 to 0.72 µg/L for iodinated DBPs and 1.36 to 3.28 µg/L for brominated DBPs. However, mono-, di-, and trichlorinated species could not be detected because the sensitivity of ICP-MS for

chlorine is poor. This method was successfully applied to measuring brominated and iodinated DBPs in drinking water, groundwater, surface water, and swimming pool water. Vincenti et al. synthesized a novel derivatizing agent, 5-chloro-2,2,3,3,4,4,5,5octafluoropentyl chloroformate (ClOFPCF), and used it for the direct derivatization of highly polar DBPs in drinking water (140). This derivatizing agent was specifically designed to derivatize carboxyl, hydroxyl, and amine groups, forming multiply substituted nonpolar derivatives that can be easily extracted from water and determined by GC/NCI-MS. The entire procedure from raw aqueous samples to ready-to-inject hexane solutions of the derivatives requires 10 ng/L in drinking water and chlorinated reservoir samples. The highest levels resulted from chlorination and ozonation. Plumlee et al. created a LC/MS/MS method for measuring six nitrosamines at low nanogram per liter levels (161). Using this method, the removal of NDMA and other nitrosamines was investigated at an advanced wastewater treatment facility that uses microfiltration, reverse osmosis (RO), and UV-H2O2. Removals using RO and UV were 24-56% and 43-66%, respectively. Finally, Zhao et al. developed a method using nano-ESI-FAIMS-MS/MS to measure seven nitrosamines in water (162). FAIMS reduced background interferences and improved the signal-to-noise as much as 10× over nano-ESIMS/MS without FAIMS. Analytical Chemistry, Vol. 82, No. 12, June 15, 2010

4761

DBPs of Pollutants. Studies of DBPs are going beyond the “classic” DBPs formed by the reaction of NOM with disinfectants, such that reactions of environmental pollutants with disinfectants are increasingly being studied. Contaminant DBPs have been recently reported from herbicides, pharmaceuticals, personal care products, microcystins, and terpenoids. Some of this research has been conducted in order to find ways to degrade and remove these contaminants from wastewater effluents and drinking water sources, but some of this research is being conducted to determine the fate of these contaminants in drinking water treatment. It is not surprising that DBPs can form from these contaminants, as many of them have activated aromatic rings or other structural groups that can readily react with oxidants like chlorine and ozone. However, until recently, these types of DBPs were not investigated. Due to the growth in this area and the potential toxicological significance of these new types of byproducts (by increasing or decreasing the toxicity/biological effect relative to the parent compound), this research area is included in this review. DBPs formed by the reaction of chlorine with triazine herbicides were the focus of an article by Brix et al. (163). UPLC-QTOF-MS/MS was used to tentatively identify four new DBPs from ametryn, prometryn, and terbutryn, which had higher toxicities than the parent herbicides. Terpenoid DBPs were the focus of another article by Joll et al., who used GC/MS to identify THMs and other DBPs formed (164). Merel et al. used linear ion trapOrbitrap-MS to identify microcystin chlorination byproducts, including four new products of microcystin-LR: chloro-microcystin, chloro-dihydroxy-microcystin, dichloro-dihydroxy-microcystin, and trichloro-hydroxy-microcystin, as well as their isomers (165). Paraben DBPs were identified by Terasaki and Makino, who used BSTFA derivatization and GC/MS to identify 14 monochloro and dichloro-parabens formed by chlorination of parabens (166). Parabens are used as preservatives in a wide variety of personal care products, including sunscreens, bath gels, shampoos, and toothpaste, and they have the potential to react with chlorine in drinking water, wastewater, or swimming pool water treatment. Ozonation products of 2-methylisoborneol were the focus of another article by Qi et al. (167). 2-Methylisoborneol is a terpenoid produced as a secondary metabolite from some cyanobacteria and actinomycetes and can cause taste and odor issues in drinking water. Camphor was identified as the primary degradation product, which was further oxidized to form other degradation intermediates, such as aldehydes, ketones, and carboxylic acids, including formaldehyde, acetaldehyde, propanal, butanal, glyoxal, and methyl glyoxal. A degradation pathway for 2-methylisoborneol was proposed, and GC/MS was used to identify the DBPs. Finally, Vanderford et al. developed a Q-TOF-MS procedure for real-time detection and identification of chlorine DBPs from organic contaminants (168). No LC separation, derivatization, or quenching of residual chlorine was required, and this method was used to identify chlorination DBPs of triclosan and atorvastatin (a cholesterol-reducing drug). In addition, as discussed earlier in the Pharmaceuticals section, several pharmaceutical DBPs have been identified, including those formed under chlorination, ozonation, chlorine dioxide, UV, and electrochemical reduction treatment (102-105). 4762


New Swimming Pool Research. Swimming pools are being recognized as an important source of exposure to DBPs. Health concerns include increased risk of bladder cancer from exposure to indoor pools and increased risk of asthma both for indoor and outdoor pools (2). The aquatic fate of sunscreen agents in model swimming pools was the focus of a study by Nakajima et al., who used GC/MS to identify the chlorination byproducts (169). Octyl-4-methoxycinnamate (OMC) and octyl-4-dimethylaminobenzoate (ODPABA) reacted with hypochlorite to produce chlorine-substituted products, which were weakly mutagenic in Salmonella (TA100). Terasaki and Makino determined chlorinated DBPs of parabens in swimming pool water using GC/MS and silylation derivatization (170). In this study of six public swimming pools, chlorinated byproducts of isopropylparaben, methylparaben, and benzylparaben were found in the waters, up to 25 ng/L. Weaver et al. used membrane ionization mass spectrometry (MIMS) to measure volatile DBPs in chlorinated indoor swimming pools (171). Eleven pools were investigated over a 6 month period, and 11 volatile DBPs were identified: monochloramine, dichloramine, trichloramine, chloroform, bromoform, bromodichloromethane, dibromochloromethane, cyanogen chloride, cyanogen bromide, dichloroacetonitrile, and dichloromethylamine. In a fascinating study involving continuous real-time measurements, Kristensen used MIMS for online monitoring of the dynamics of THM concentrations in a warm public swimming pool (172). The MIMS instrument performed unsupervised for more than a year, with only short interruptions for filament replacements every 6-8 weeks. Online monitoring revealed the daily cycles of chloroform and bromodichloromethane concentrations, which increased during the pools’ closing hours and decreased during opening hours. Daily concentrations of 30-100 µg/L for chloroform were observed, and 5-10 µg/L levels of bromodichloromethane were observed, except for short bursts in bromodichloromethane levels (up to 100 µg/L) that were linked to salt addition (sodium chloride) used to electrolytically generate chlorine for disinfection. Lower THM levels correlated to the operation of a strong water jet system. SUNSCREENS/UV FILTERS UV filters used in sunscreens, cosmetics, and other personal care products have increased in interest due to their presence in environmental waters and their potential for endocrine disruption and developmental toxicity. A few UV filters have been shown to have estrogenic effects similar to E2 (a natural estrogen), as well as the potential for developmental toxicity (2). Levels observed in environmental waters are not far below the doses that cause toxic effects in animals. There are two types of UV filters, organic UV filters, which work by absorbing UV light, and inorganic UV filters (TiO2, ZnO), which work by reflecting and scattering UV light. Organic UV filters are increasingly used in personal care products, such as sunscreens, cosmetics, beauty creams, skin lotions, lipsticks, hair sprays, hair dyes, and shampoos. Examples include benzophenone-3 (BP-3), 4-hydroxybenzophenone (HBP), 2-hydroxy-4-methoxylbenzophenone (HMB), 2,4dihydroxybenzophenone (DHB), 2,2′-dihydroxy-4-methoxybenzophenone (DHMB), 2,3,4-trihydroxybenzophenone (THB), octyldimethyl-p-aminobenzoic acid (ODPABA), 4-methylbenzylidene camphor (4-MBC), ethylhexyl methoxycinnamate (EHMC),

octyl methoxycinnamate (OMC), octocrylene (OC), butyl methoxydibenzoylmethane (BM-DBM), terephthalylidine dicamphor sulfonic acid (TDSA), ethylhexyl triazone (EHT), phenylbenzimidazole sulfonic acid (PBSA), ethylhexyl salicylate (EHS), benzhydrol (BH), and 1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)-1,3-propanedione (BPMP). The majority of these are lipophilic compounds (low water solubility) with conjugated aromatic systems that absorb UV light in the wavelength range of 290-320 nm (UVB) and/or 320-400 nm (UVA). Most sunscreen products contain several UV filters, often in combination with inorganic micropigments. Because of their use in a wide variety of personal care products, these compounds can enter the aquatic environment indirectly from bathing or washing clothes, via wastewater treatment plants and directly from recreational activities, such as swimming and sunbathing in lakes and rivers. Diaz-Cruz et al. published a nice review of organic UV filters, with a focus on their photodegradates, metabolites, and DBPs formed in swimming pools (173). Chemical structures of the parent UV filters and their metabolites/degradation products are also included, along with their chemical properties. Another review by Diaz-Cruz and Barcelo´ discussed analytical methods for and ecotoxicological effects of UV filters (174). New methods continue to be developed, including ones using UPLC, APPI, SPME, and matrix solid-phase dispersion (MSPD). For example, Nieto et al. created a method using UPLC/ESI-MS/ MS to measure four UV filters and other personal care products in sewage sludge (175). Pressurized liquid extraction (PLE) was used for extraction, and the entire process took a total of 39 min. Limits of detection were 10 times higher than in Germany. U.S. levels ranged from 321 to 3073 ng/g and German levels ranged from 330 to 2069 ng/g. PBDEs were found in all samples, indicating that dryer lint may be a source of PBDE exposure. It was suggested that dryer electrical components and/or dust from clothing may be contributors. Air from computer classrooms was investigated by Cheng et al. (183). Six air samples collected from three classrooms were measured using GC/high resolution-MS. When computers were turned on, the total PBDE concentration was 10-fold higher than when they were switched off. Contribution from other sources (including wall paper, plastic laminate flooring materials, and chairs with polyurethane foam) was also observed. In the study of Tasmanian devils, Vetter et al. compared GC/ high resolution-EI-MS and GC/NCI-MS/MS with isotope dilution to measure polybrominated biphenyls (PBBs) in tissue samples from diseased and nondiseased animals (184). Both techniques verified concentrations of PBB-153 at levels of 0.3-11 ng/g lipid, and the PBB residue pattern revealed that the source originated from a technical grade hexabromobiphenyl, which is dominated by PBB-153. Other congeners (e.g., PBB-132 and PBB-138) were also detected but at lower levels. No differences were observed in levels between the diseased and nondiseased animals. Concentrations of PBBs were considered remarkable because they were never produced in Australia, and Tasmanian devils feed at a lower trophic level compared to top predators, such as killer whales. Tasmanian devils were listed as an endangered species in 2008, due to a viral epidemic that has killed half of the population, and this study was undertaken to investigate their contamination status in the course of investigating causes for the disease. 4764


Marine biota was the focus of a study by Kato et al., who used LC/APCI-MS/MS to measure hydroxylated and methoxylated PBDE metabolites (185). Concentrations in tiger shark and bull shark liver samples were up to 8 ng/g (lipid weight) for hydroxylated PBDEs and up to 540 ng/g for methoxylated PBDEs. This study also reported the first detection of 2,2′-dihydroxy3,3′,5,5′-tetrabromobiphenyl in marine sponge from Micronesia. LC/MS/MS provided advantages over GC/MS by enabling a rapid and simultaneous determination of hydroxylated and methylated PBDEs and their analogues in a single preparation step, without the use of derivatization. Tadeo et al. developed a method for measuring PBDEs in human hair and measured them in samples from 16 individuals (186). Hair samples were digested with HCl, extracted with hexane, and measured by GC/MS, at detection limits of 0.08-0.9 ng/g. Five PBDEs (BDE-209, BDE-47, BDE99, BDE-100, and BDE-190) were found in most samples, with BDE-209 being the dominant one and total PBDE levels ranging from 1.4 to 19.9 ng/g. Qiu et al. used GC/NCI-MS to measure PBDEs and hydroxylated PBDE metabolites in human blood from pregnant women and their newborn babies in the United States (187). In the 20 samples collected, the metabolite pattern of the hydroxylated PBDEs was found to be much different in human blood than what has been found in the blood of mice. In addition, the ratio of total hydroxylated metabolites relative to their PBDE precursors ranged from 0.10 to 2.8, indicating that hydroxylated metabolites of PBDEs were accumulating in human blood. New methods for measuring brominated flame retardants include those using APPI, ICP-MS, high resolution-MS, and lowpressure GC/MS. For example, Abdallah et al. created a new 13Clabeled isotope dilution-LC/APPI-MS/MS method to measure PBDEs in household dust (188). Fourteen PBDEs (tetra- to deca-bromo) were included, and method detection limits ranged from 12 to 30 pg. Swarthout et al. developed a new method using GC/ICP-MS to measure PBDEs in mussel tissue and marine sediment (189). The GC/ICP-MS method was found to be more sensitive than GC/NCI-MS and allowed detection limits of 0.2-0.3 pg, as compared to 1.5-24.3 pg with GC/NCI-MS. Lacorte et al. reported a new GC/high resolutionMS method to measure PBDEs (mono- to deca-bromo) and their hydroxylated and methoxylated metabolites in sediment, fish tissue, and milk (190). PLE was followed by gel permeation chromatography and florisil cleanup, and 11 target and 35 nontarget hydroxylated and methoxylated PBDEs were determined. Limits of quantification were 3.28 pg/g dry weight, 20.5 pg/g lipid weight, and 41.4 pg/g lipid weight in sediment, milk, and fish, respectively. This method was used to measure these analytes in sediments from British Columbia, fish purchased at a local supermarket, and breast milk. Sediment levels reached 1249 pg/g dry weight (BDE-209), milk levels reached 204 pg/g lipid weight (BDE-183), trout levels reached 60,011 pg/g lipid weight (BDE-47), and herring levels reached 4924 pg/g lipid weight (BDE-47). Several hydroxylated and methoxylated PBDEs were also tentatively identified in the sediment and fish samples. Dirtu et al. created a new low pressure-GC/ NCI-MS method to measure decabrominated diphenyl ether (BDE-209) and other PBDEs in dust samples (191). Low pressure-GC (which resulted in a lower elution temperature)

was used to avoid thermal decomposition that can happen for BDE-209 using conventional GC/MS techniques. A wide bore GC column (0.53 mm i.d., 0.15 µm film thickness) and a 1 m × 0.1 mm i.d. short restriction column on the inlet end provided the low pressure conditions that allowed good separation of 22 major PBDE congeners in 12 min, minimal degradation of BDE-209, and detection of BDE-209 down to 0.06 pg. Studies continue to explore the fate of PBDEs in the environment. For example, Robrock et al. investigated the aerobic biotransformation of PBDEs in bacteria using GC/ECD and GC/ MS (192). Two PCB-degrading strains of bacteria were found to transform all of the mono- through penta-BDEs, and one strain transformed one of the hexa-BDEs. The extent of transformation was inversely proportional to the degree of bromination. This is the first report of aerobic transformation of these PBDEs, as well as the first report of the stoichiometric release of bromide during PBDE transformation. BENZOTRIAZOLES Benzotriazoles are complexing agents that are widely used as anticorrosives (e.g., in engine coolants, aircraft deicers, or antifreeze liquids) and for silver protection in dish washing liquids. The two common forms, benzotriazole and tolyltriazole, are soluble in water, resistant to biodegradation, and are only partially removed in wastewater treatment. There is also new evidence for estrogenic effects in vitro but, so far, not in vivo, in recent fish studies (2). Because of their water solubility, LC/MS and LC/ MS/MS methods have been recently developed for their measurement in environmental waters. While reports of benzotriazoles are fairly recent (last 5 to 6 years), studies indicate that they are likely ubiquitous environmental contaminants. Benzothiazoles and benzosulfonamides are also increasingly being measured in environmental samples. Benzothiazoles are high production chemicals used as corrosion inhibitors, biocides in paper and leather manufacturing, and in the production of rubber (193). Benzosulfonamides are widely used as plasticizers and intermediates in the synthesis of sweeteners and can be metabolites of corrosion inhibitors (193). New methods developed include one by Jover et al. who investigated the use of GC × GC-TOF-MS to measure benzotriazoles, benzothiazoles, and benzosulfonamides in environmental waters (193). SPE was used for extraction, and GC × GC improved separations, enabling the identification of minor components that might be overlooked with other methods. This method was then used to measure these analytes in river water, effluent from a wastewater treatment plant, and raw sewage. Orbitrap-MS was used in another method by van Leerdam et al., who measured six benzotriazoles and benzothiazoles in water (194). This LC/ linear ion trap-Orbitrap-MS method enabled improved mass accuracies and detection limits down to 0.01 µg/L. The occurrence and fate of benzotriazoles and benzothiazoles in constructed wetlands and a wastewater treatment plant was investigated by Matamoros et al., who used GC × GC-TOF-MS (195). Benzotriazole removal efficiencies ranged from 65 to 70% and 89 to 93% in the conventional wastewater treatment plant and in the constructed wetlands, respectively. Benzothiazole removal efficiencies ranged from 0 to 80% and 83 to 90% in the conventional wastewater treatment plant and in the constructed wetlands, respectively. Higher degradation in the constructed wetlands was

attributed to the possibility of biodegradation, photodegradation, and plant uptake. DIOXANE 1,4-Dioxane is a widespread industrial contaminant in environmental waters (often exceeding water quality criteria and guidelines), has also been found in drinking water, and is a probable human carcinogen. Dioxane is a high production chemical and is used as a solvent stabilizer in the manufacture and processing of paper, cotton, textile products, automotive coolants, cosmetics, and shampoos, as well as a stabilizer in 1,1,1trichloroethane (TCA), a popular degreasing solvent. In 2002, more than 500 t of dioxane were produced or imported in the United States (2). The U.S. EPA has identified dioxane as a high priority contaminant, and it is currently listed on the new CCL-3 (www.epa.gov/safewater/ccl). Dioxane is problematic to extract and measure because it is miscible with water. It is also difficult to remove from water by air stripping or carbon adsorption. Household detergents and cleaners were the focus of a new study by Tanabe and Kawata, who used GC/MS (196). Dioxane was detected in 40 out of the 51 samples investigated, including products containing anionic surfactants. The dioxane load per person in Japan was calculated to be 0.061 mg/day/person. SILOXANES Siloxanes are becoming an intense area of research, and as such, they are included in this review for the first time. They include cyclic siloxanes, octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), dodecamethylcyclohexasiloxane (D6), and tetradecamethylcycloheptasiloxane (D7), and linear siloxanes, which are used in a number of products, such as cosmetics, deodorants, soaps, hair conditioners, hair dyes, car waxes, baby pacifiers, cookware, cleaners, furniture polishes, and water-repellent windshield coatings. There is concern about potential toxicity and transport into the environment. Horii and Kannan conducted an extensive survey of siloxanes in a variety of consumer products, including hair-care products, skin lotions, body washes, cosmetics, baby pacifiers, cookware, household cleaners and furniture polishes (197). D4, D5, D6, and D7 were measured, as well as linear siloxanes (L4 to L14), using GC/MS. Liquid samples were mixed thoroughly; solid samples were cut into small pieces, and both were extracted using ethyl acetate/hexane. Concentrations of the cyclic siloxanes were found up to 9380, 81 800, 43 100, and 846 µg/g for D4, D5, D6, and D7, respectively. Concentrations of linear siloxanes ranged from 97% of n-butylcyclohexylbutanoic acid was transformed in 30 days, whereas a highly branched isomer (tert-butylcyclohexylbutanoic acid) was only transformed by 2.5%. It was suggested that bacteria capable of oxidizing branched NAs or attacking the cyclic rings should be sought out to achieve remediation of these recalcitrant NAs. TiO2 and irradiation with fluorescent and natural sunlight were investigated by Headley et al. as a means to degrade NAs (208). Under natural sunlight irradiation over the TiO2 suspension, ∼75% of the compounds in the commercial NA mixture and 100% of 4-methylcyclohexaneaceticic acid (4-MCHAA, a candidate NA) were degraded in 8 h. No degradation was observed in the dark. Ozonation was investigated by Scott et al., who treated oil-sands process water with ozone for 50 min (209). Following ozonation, NAs decreased by 70%, and treated waters were not toxic (in the Microtox assay). After 130 min of ozonation, the residual NA concentration (2 mg/L) was 99% degradation was achieved after 8 min of treatment with both UV and UV/H2O2; for wastewater, UV irradiation alone allowed 93% removal and UV/H2O2 allowed >99% removal.

PESTICIDE TRANSFORMATION PRODUCTS AND NEW PESTICIDES Herbicides and pesticides continue to be the focus of much environmental research. Recent studies have focused more on their transformation products because their hydrolysis, oxidation, biodegradation, or photolysis transformation products can be present at greater levels in the environment than the parent pesticide and can be as toxic or more toxic. New pesticides have also come on the market (such as glyphosate, organophosphorus herbicides, and azole fungicides), and studies are being conducted to understand their fate and transport in the environment. Several pesticide degradation products are on the U.S. EPA’s new CCL3: alachlor ethanesulfonic acid (ESA), alachlor oxanilic acid (OA), acetochlor ESA, acetochlor OA, metolachlor ESA, metolachlor OA, 3-hydroxycarbofuran, and terbufos sulfone (www.epa.gov/safewater/ccl), as well as on the UCMR-2 (alachlor ESA and OA, acetochlor ESA and OA, and metolachlor ESA and OA). LC/MS and LC/MS/MS are now commonplace for measuring pesticide degradates, which are generally more polar than the parent pesticides, making LC/MS ideal for their detection. In addition, researchers are increasingly using UPLC to enable simultaneous analysis of larger groups of pesticides, and TOFMS and Q-TOF-MS are being used to identify new pesticide degradates. Hernandez et al. published a nice review of the use of LC/TOF-MS for identifying and quantifying pesticide metabolites in food and water (217). Benefits include high sensitivity in full-scan acquisition mode and increased mass accuracy, which allows not only reliable quantification (and confirmation) of target analytes but also the opportunity to identify new, nontarget analytes, within the same MS run. Soler et al. discussed the role of LC/MS in pesticide and pesticide degradate determination in foods, which included a discussion of problems, such as matrix effects (218). Different types of mass spectrometers were covered, as well as recent applications. Vidal et al. published an extensive review on extraction and detection methods for pesticide transformation products in environmental, biological, and food samples and included a discussion of problems that can be encountered with their extraction (219). The analysis of target analytes as well as the identification of unknown compounds with high resolutionMS are also discussed, and a comprehensive listing of >100 transformation products of 49 different pesticides is provided. New methods include several using UPLC. For example, Kovalczuk et al. developed a rapid, high-throughput UPLC/MS/ MS method to measure 64 pesticides and their metabolites in fruit extracts (220). The total time required for analysis was 8 min, plus 2 min for re-equilibration back to the initial UPLC conditions. Quantification limits of 80%). Concentrations of azole fungicides used as pesticides or as biocides (propiconazole and tebuconazole) were found up to 40 and 10 ng/L, respectively, in wastewater effluents. Concentrations of azole fungicides used as pharmaceuticals (fluconazole and clotrimazole) were found up to 83 and 6 ng/L, respectively, in wastewater effluents. In lakes, fluconazole, propiconazole, and tebuconazole were detected at low nanogram per liter levels, up to a maximum of 9.0, 1.9, and 1.0 ng/L, respectively. Chiron et al. measured pesticides and their transformation products in southern France (225). MCPA [(4-chloro-2-methylphenoxy)acetic acid] was found to transform by photolysis according to the following sequence: MCPA f 4-chloro-2-methylphenol (CMP) f 4-chloro-2-methyl-6-nitrophenol (CMNP). CMNP was more environmentally persistent than the parent compound. While nitration of chlorophenols typically reduces their acute toxicity, there is concern over the genotoxic effects of nitro compounds. Irradiation experiments suggested that the photonitration of CMP to CMNP involved nitrogen dioxide, generated from the photolysis of nitrate and photooxidation of nitrite by OH radical. Fe(III) is also believed to play a role. The fate of metolachlor and metolachlor ESA in surface waters in Lake Greifensee, Switzerland, was investigated by Huntscha et al. (226). The two compounds showed distinctly different concentration dynamics in the lake tributaries, such that 70% of the yearly load of metolachlor ESA to the lake was from groundwater recharge, whereas for metolachlor, 50-80% was from event-driven runoff. Photolysis was a dominant reaction pathway during the summer months, with half-lives of approximately 100-200 days, along with a potential contribution of biodegradation. 4768


PERCHLORATE Perchlorate became an important environmental issue following its discovery in a number of water supplies in the western United States. It has since been found in environmental waters across the United States and in other parts of the world at microgram per liter levels, as well as in fresh produce, foods, wines, and beverages from many countries, including those in Europe and the Far East. Perchlorate has also been found in biological samples, and it can be transported by pregnant mothers to their developing baby across the placental barrier. Perchlorate is increasingly being found in environmental waters following fireworks displays. As a result, it is now recognized as a worldwide environmental issue, rather than only being limited to the United States. Ammonium perchlorate has been used in solid propellants used for rockets, missiles, and fireworks, as well as highway flares. There is also potential contamination from fertilizers (e.g., Chilean nitrate, where perchlorate co-occurs naturally), and new work has revealed other natural sources of perchlorate. In addition, recent studies have shown that perchlorate can be a contaminant in sodium hypochlorite (liquid bleach) that is used in drinking water treatment. Perchlorate is an anion that is very water-soluble and environmentally stable. It can accumulate in plants (including lettuce, wheat, and alfalfa), which can contribute to exposure in humans and animals. In addition, perchlorate is not removed by conventional water treatment processes, so human exposure can also come through drinking water. Health concerns arise from perchlorate’s ability to displace iodide in the thyroid gland, which can affect metabolism, growth, and development. Due to these concerns, the U.S. EPA placed perchlorate on the U.S. EPA’s CCL (CCL-1 and CCL-2 and, now, on the CCL-3; www.epa.gov/ safewater/ccl). Perchlorate was also included in the first UCMR (www.epa.gov/safewater/ucmr). The U.S. EPA established a reference dose of 0.0007 mg/kg/day, which translates to a drinking water equivalent level (DWEL) of 24.5 µg/L (www. councilonwaterquality.org/issue/regulation.html). In 2004, the State of California became the first state to set a drinking water public health goal (6 µg/L), and at least seven other states have issued advisory levels ranging from 1 to 18 µg/L (www.epa.gov/ fedfac/documents/perchlorate_links.htm#state_adv). In October 2007, California issued a new regulation for perchlorate in drinking water, with an MCL of 6 µg/L (www.cdph.ca.gov/certlic/ drinkingwater/Pages/Perchlorate.aspx). There are now several EPA Methods for measuring perchlorate in water, including a new one (EPA Method 314.2) that uses twodimensional IC with suppressed conductivity detection (www. epa.gov/safewater/methods/analyticalmethods_ogwdw.html) and has a 55 ng/L detection limit. Parker reviewed the occurrence of perchlorate in the environment and provided evidence of widespread natural occurrence (227). Furdui and Tomassini published a fascinating study of trends and sources of perchlorate in Arctic snow (228). Samples from the Devon Island ice cap in Canada were used to calculate the annual input of atmospherically formed perchlorate. Ice cores were dated between 1996 and 2005, and IC/ESI-MS/MS was used for measurement. Concentrations varied between 1 and 18 ng/L and were correlated with total ozone levels from this area. Data suggested that perchlorate from the Arctic snow was formed in the atmosphere by two different mechanisms: (1) Stratospheric

chlorine radicals reacted with ozone year round, producing concentrations of perchlorate correlated with the total ozone level; (2) During the summer months, perchlorate was likely formed in the troposphere. Interestingly, a deep ice core sample revealed that perchlorate was present in precipitation at similar concentrations more than 2000 years ago. The total estimated amount that reached the Arctic in 2005 was 41-86 t. Wang et al. measured perchlorate in 150 different fruit and vegetables purchased from stores in Ottawa, Canada, that were from Canada or imported from many different countries (229). IC/MS/MS was used for measurement. Perchlorate was found in most of the tested foods, ranging up to 536 µg/kg. The highest levels included cantaloupes from Guatemala (156 µg/kg), spinach from the United States (133 µg/kg), green grapes from Chile (45.5 µg/kg), and Romaine lettuce from the United States (29.1 µg/ kg). Dietary exposure was estimated at approximately 36.6 and 41.1 ng/kg body weight/day for toddlers (1-4 years) and children (5-11 years), respectively. Another large occurrence study of perchlorate and chlorate was in beverages in Japan, also using IC/MS/MS for measurement (230). More than 100 bottled beverages were purchased in the Tokyo area. Perchlorate was detected in 62 beverages, up to 0.92 µg/L, and chlorate was detected in 85 beverages, up to 700 µg/L. Dried blood spots from newborns were the focus of a study by Otero-Santos et al., who used IC/MS/MS to measure perchlorate (231). Quantification limits of the method were 0.10 ng/mL. Perchlorate was detected in 100% of the blood spots collected from 100 newborns, with a median blank-adjusted concentration of 1.88 ng/mL. In another extensive human exposure study, Blount et al. assessed prenatal exposure of perchlorate, thiocyanate, and nitrate in mothers and newborns from New Jersey (232). Maternal and fetal fluids were collected during cesarean-section surgeries of 150 U.S. women, and IC/MS/MS was used for measurement. Geometric means of perchlorate, thiocyanate, and nitrate in maternal urine were 2.90, 947, and 47 900 µg/L, respectively. Perchlorate was detected in most samples: urine (100%), maternal serum (94%), cord serum (67%), and amniotic fluid (97%). However, no evidence of disproportionate perchlorate accumulation or lack of iodide in the fetal compartment was found, and there was no association between cord blood levels and newborn weight, length, or head circumference. Finally, Oldi and Kannan developed a method for measuring perchlorate in human saliva, using 18O perchlorate isotope dilution, ultrafiltration, and LC/ MS/MS (233). The method quantification limit was 0.4 ng/ mL. Perchlorate was then measured in the saliva from 83 people in New York, where levels ranged from 0.4 to 37 ng/ mL, with a mean of 5.3 ng/mL. ALGAL TOXINS Algal toxins (mostly cyanobacterial toxins produced from bluegreen algae) continue to be of increasing interest in the United States and in other countries around the world. Increased discharges of nutrients (from agricultural runoff and from wastewater discharges) have led to increased algal blooms and an accompanying increased incidence of shellfish poisoning, large fish kills, and deaths of livestock and wildlife, as well as illness and death in humans. Toxins produced by these algae have been implicated in the adverse effects. The most commonly occurring algal toxins are microcystins, nodularins, anatoxins, cylindrosper-

mopsin, and saxitoxins. “Red tide” toxins are also often found in coastal waters. Microcystins and nodularins are hepatotoxic high molecular weight, cyclic peptide structures. Anatoxins, cylindrospermopsin, and saxitoxins are heterocyclic alkaloids; anatoxins and saxitoxins are neurotoxic, and cylindrospermopsin is hepatotoxic. “Red tide” toxins include brevetoxins, which have heterocyclic polyether structures and are neurotoxic. Microcystins (of which, more than 70 different variants have been isolated and characterized) are the most frequently reported of the algal toxins. The most common microcystins are cyclic heptapeptides that contain the amino acids leucine and arginine in their structures. Nearly every part of the world that uses surface water as a drinking water source has encountered problems with cyanobacteria and their toxins. Algal toxins were on the U.S. EPA’s previous CCLs (CCL-1 and CCL-2) in a general way, “cyanobacteria (bluegreen algae, other freshwater algae, and their toxins)”, and now, the CCL-3 has specifically named three cyanobacterial toxins: anatoxin-a, microcystin-LR, and cylindrospermopsin for the new list (www.epa.gov/safewater/ccl). Several countries, including Australia, Brazil, Canada, France, and New Zealand have guideline values for microcystins, anatoxin-a, and cylindrospermopsin (ranging from 1.0 to 1.5 µg/L). The European Drinking Water Directive has a guideline of 0.1 µg/L. Many of these toxins have relatively high molecular weights and are highly polar. New methods for algal toxins include those using UPLC/MS and matrix-assisted laser desorption ionization (MALDI)-TOF-MS. Trends in research include an increase in environmental fate studies of algal toxins, including the identification of products from biodegradation, chlorination, and treatment with TiO2/UV photocatalysis. Christian and Luckas published an excellent review on the occurrence, toxicity, and analysis of marine toxins (234). Several classes of marine biotoxins were discussed, including paralytic shellfish poisoning (PSP) toxins, diarrhetic shellfish poisoning (DSP) toxins, azaspiracid poisoning (AZP) toxins, amnesic shellfish poisoning (ASP) toxins, tetrodotoxins, and ciguartera. Chemical structures of many of these toxins were presented, as well as LC/MS/MS and biological methods for their measurement. New methods include one by Meisen et al. that coupled thin layer chromatography (TLC) and UV spectroscopy with infrared (IR)-MALDI-TOF-MS to measure microcystin-LR and nodularin (235). Detection limits were 5 ng for UV and 3 ng for MS. Xu et al. created a new direct injection-UPLC-ESI-MS/MS method for measuring seven microcystins in environmental waters (236). Limits of detection and quantification were 0.06 and 0.2 µg/L, respectively. The method required no preconcentration step, only filtration before UPLC/MS analysis. Using this method, microcystins were detected in polluted lake waters in Eastern China, with microcystin-RR and -LR most predominant, up to 70 µg/L. Anatoxin-a poisoning in dogs was the focus of a study by Puschner et al., who investigated two incidents involving river water from California and pond water from Ontario, Canada (237). In the first incident in California, three dogs developed seizures and died within an hour after swimming in a river, and in the second, three dogs died within 1 h after swimming in a pond in Ontario. Anatoxin-a was isolated from these environmental waters and in the stomach contents of the dogs using LC/MS/MS. The presence of other potential contaminants was also investigated using GC/MS, including the pesticide zinc phosphide, organoAnalytical Chemistry, Vol. 82, No. 12, June 15, 2010

4769

phosphorus and carbamate insecticides, strychnine, and micotoxins. None of these toxicants were detected, but LC/MS/MS revealed the presence of anatoxin-a, which represented the first documented case of anatoxin-a poisoning in dogs in North America. In another study, Zhang et al. used LC/ESI-MS to measure three microcysins (microcystin-RR, -YR, and -LR) in six species of fish in Lake Taihu, China (238). Liver and gut concentrations were highest in phytoplanktivorous fish (up to 233.5 µg/g dry weight), followed by omnivorous fish (up to 73.27 µg/g dry weight), and carnivorous fish (up to 0.047 µg/g dry weight), while levels in the muscle were highest in the omnivorous fish, followed by phytoplanktivorous fish, and carnivorous fish. This study was also the first to demonstrate microcystin accumulation in the gonads of wild fish. Another interesting study by Rellan et al. involved the first detection of anatoxin-a in dietary supplements containing cyanobacteria (239). Thirty-nine different dietary supplements were evaluated, and LC/fluorescence and GC/MS were used to measure anatoxin-a. Three samples, one a human dietary supplement and the other two fish and bird dietary supplements, contained anatoxin-a, at levels ranging from 2.50 to 33 µg/g. Several good fate studies have been published recently. For example, Mazur-Marzec investigated the biodegradation of nodularin and the effects of this toxin on bacterial isolates from coastal waters off Poland (240). LC/Q-TOF-MS was used to identify the degradation products, which included five new ones not previously reported. Microorganisms living in the Baltic Sea sediments removed nodularin within 5-7 days. Chlorination byproducts of microcystin-LR were the focus of a new study by Merel et al., who used linear ion trap-Q-Orbitrap-MS to identify the products (241). Microcystin-LR was totally transformed within 2 min, and eight new byproducts were identified, including chloro-microcystin, chloro-dihydroxy-microcystin, dichloro-dihydroxy-microcystin, trichloro-hydroxy-microcystin, and several dihydroxy-microcystins. Finally, in a study by Antoniou et al., TiO2/UV photocatalysis was used to degrade microcystin-LR, and LC/MS/MS was used to identify intermediates formed during this process (242). Most of these intermediates have not been reported in previous studies. Results showed that microcystin-LR degradation is initiated at four sites on the toxin: three sites on the Adda amino acid (aromatic ring, methoxy group, and conjugated double bonds) and one on the cyclic structure (Mdha amino acid). Several other geometric isomers were also formed. The reactions involved hydroxyl radical addition/substitution, oxidation, and bond cleavage. This is the first study to report the hydroxylation of the aromatic ring and the demethoxylation of microcystin-LR with TiO2/UV. Detailed reaction mechanisms are proposed for the formation of these intermediates, which still have rather high molecular weights (>750 Da). MICROORGANISMS Outbreaks of waterborne illness in the United States and other parts of the world have necessitated improved analytical methods for detecting and identifying microorganisms in water and other environmental samples. Several microorganisms are included on the new CCL-3 (www.epa.gov/safewater/ccl) (Table 2). The U.S. EPA’s National Exposure Research Laboratory in Cincinnati has developed several methods for measuring microorganisms in water (www.epa.gov/nerlcwww). These include methods for 4770


Cryptosporidium, Giardia, E. coli, Aeromonas, coliphages, viruses, total coliforms, and enterococci. E. coli O157:H7 and H1N1 (swine flu) are currently capturing a lot of attention because they have caused a number of outbreaks and deaths around the world. Traditional biological methods are often used for detection of microorganisms, including cell culture, immunological methods, polymerase chain reaction (PCR), and microscopic identification, but ESI and MALDI-MS methods are also often used. Two recent reviews highlight the use of mass spectrometry for characterizing microorganisms. Demirev and Fenselau discuss successful mass spectrometry approaches that involve the detection of organism-specific biomarkers, which allow the differentiation between different organisms (243). The biomarkers include intact proteins, their proteolytic peptides, and nonribosomal peptides. The combined use of proteome searching and tandemMS allows the unambiguous identification of individual biomarker proteins, which enable the source microorganism to be identified. The use of ESI and MALDI with TOF, FT, and ion trap mass spectrometers is discussed, as well as sample preparation. In another review, Sauer and Kliem highlight mass spectrometry methods for identifying bacteria (244). They included discussions of MALDI and ESI used with TOF-MS/MS to identify protein mass patterns, nucleic acids, and PCR products. The authors viewed the most promising ESI-MS method for detecting microorganisms to be the combination of nucleic acid amplification of bacterial genome loci with high resolution-ESI-MS detection of PCR products and base composition analysis. The authors also reported results from an international validation study of the MALDI-MS-based protein pattern detection approach, where 98.75% interlaboratory reproducibility was demonstrated for 60 blind-coded bacterial samples. CONTAMINANTS ON THE HORIZON: MELAMINE-CYANURIC ACID Melamine-Cyanuric Acid. In early 2007, a pet food scare gripped in the United States, where hundreds of pets, especially cats, were dying of renal failure. Crystals of a melamine-cyanuric acid complex (1:1) in the pet food were determined to be the cause. Later, in 2008, contamination of infant formula was discovered, which resulted in serious illness and death in babies in China, and later research revealed contamination in other animal feeds (chicken, hogs, and fish). Following intense investigations, it was found that the melamine and cyanuric acid were deliberately added to wheat gluten products from China, which made their way into several food products, including pet foods, chicken feed, and infant formula. It is suspected that the melamine and cyanuric acid originated as industrial waste products, which can be byproducts from the production of plastics, pesticides, plant fertilizers, paints, building materials, paper, or textiles. Because both melamine and cyanuric acid have significant nitrogen content (especially melamine), they can masquerade as nitrogen in proteins in simple total nitrogen assays. Originally, melamine alone was believed to be responsible for these adverse effects, but later, it was determined that cyanuric acid must also be present to form these crystals. Melamine and cyanuric acid have a strong affinity for each other, forming a nearly insoluble melamine-cyanurate complex. Thus, melamine by itself is not believed to cause significant health issues, but the crystals formed by the combina-

tion of melamine with cyanuric acid (both triazine-based molecules) can be lethal. It is not known at this time whether there will be other environmental effects or whether this will ever be a problem in the future, but because of the significant adverse health effects resulting from this deliberate contamination, I am including this contaminant in this review for the first time. Tyan et al. published a review of methods for measuring melamine in food and included a discussion of the melamine issue, its chemical properties, toxicity, and risk assessment (245). Already, there are many methods that have been developed in the last 2 to 3 years since the initial pet food contamination. Methods include GC/MS, LC/MS(/MS), UPLC/MS/MS, MALDITOF-MS, LC-diode array, direct analysis in real time (DART)-MS, enzyme-linked immunosorbent assay (ELISA), and low-temperature plasma-MS/MS. However, most of these methods were developed to measure melamine only and not the combination of melamine and cyanuric acid within a single method. As a result, a new method was developed by Heller and Nochetto (from the U.S. Food and Drug Administration (FDA) Center for Veterinary Medicine) using zwitterionic (ZIC)-HILIC/ESI-MS/MS to measure melamine and cyanuric acid simultaneously in animal feed (246). This method can measure melamine and cyanuric acid, whether they are present individually or as the complex, down to 0.5 µg/ g, in a single run. ZIC-HILIC columns incorporate a silica-bonded alkyl group with both a cationic site (quaternary nitrogen) and an anionic site (sulfonate), which allowed good separation of melamine and cyanuric acid with a combined HILIC and pH gradient. Three MS/MS transitions were monitored for each compound using a triple quadrupole mass spectrometer. Ibanez et al. published a LC/ESI-MS/MS method for measuring melamine in a variety of foods, including several milk-based products (247). This method involves the extraction with aqueous trichloroacetic acid (1%), 10-fold dilution, and injection into to the LC/MS system, with isotopically labeled melamine as an internal standard. Detection limits of 0.01-0.1 mg/kg were achieved. Catfish, trout, tilapia, salmon, and shrimp were the focus of a new method by Andersen et al., which investigated the uptake of melamine in these fish that were fed melamine-contaminated food (248). Tissues were extracted with acidic acetonitrile, defatted with dichloromethane, cleaned up using mixed-mode cation exchange SPE cartridges, and analyzed using LC/ESI-MS/MS with hydrophilic interaction chromatography. After feeding these fish 400 mg/kg of melamine or a melamine-cyanuric acid, all edible tissues of the fish were found to contain melamine residues, up to 210 mg/kg. This method was also used to determine melamine levels in >100 shrimp, catfish, tilapia, salmon, eel, and other types of fish purchased from seafood markets. Thirty-three samples were positive for melamine, and 10 had levels >50 µg/kg. Tittlemier et al. used SPE with LC/MS/MS to measure 94 samples of infant formula purchased from major retailers in Ottawa, Ontario (249). Melamine was detected in 71 of the 94 products, at levels ranging from 4.31 to 346 ng/g (median of 16 ng/g), which do not pose a health risk. Tang et al. used a MALDIMS method to analyze melamine-cyanurate in urinary stones/ residues from patients who had kidney stones associated with the consumption of melamine-tainted food products (250). The

method developed was simple and rapid. Sample preparation involved a wash with water, and the time of sample treatment to analysis was

Environmental Mass Spectrometry: Emerging ... - ACS Publications

Recommend Documents