AnalyticalMethods

TECHNICAL NOTE

Publ

ishe

d on

13

Mar

ch 2

014.

Dow

nloa

ded

by U

nive

rsity

of

Vic

tori

a on

27/

10/2

014

12:5

0:50

.

View Article OnlineView Journal | View Issue

aEmergency Response Branch, Division of L

Environmental Health, Centers for Diseas

Highway, MS F-44, Atlanta, Georgia 30341,bU.S. Environmental Protection Agency, Nati

26 W. Martin Luther King Drive, MS NG16,

† Present Address: Department of Pharma& Health Sciences, Mercer University, 30030341, USA.

Cite this: Anal. Methods, 2014, 6, 2780

Received 29th October 2013Accepted 24th February 2014

DOI: 10.1039/c3ay41912f

www.rsc.org/methods

2780 | Anal. Methods, 2014, 6, 2780–2

Quantitative analysis and stability of therodenticide TETS (tetramine) in finished tap water

Jennifer S. Knaack,†a Elizabeth I. Hamelin,a Matthew Magnuson,b Erin Silvestri,b

Doris Asha and Rudolph C. Johnson*a

The determination of the rodenticide tetramethylenedisulfotetramine (TETS) in drinking water is reportable

through the use of automated sample preparation via solid phase extraction and detection using isotope

dilution gas chromatography-mass spectrometry. The method was characterized over twenty-two

analytical batches with quality control samples. Accuracies for low and high concentration quality

control pools were 100 and 101%, respectively. The minimum reporting level (MRL) for TETS in this

method is 0.50 mg L�1. Five drinking waters representing a range of water quality parameters and

disinfection practices were fortified with TETS at ten times the MRL and analyzed over a 28 day period to

determine the stability of TETS in these waters. The amount of TETS measured in these samples

averaged 100 � 6% of the amount fortified suggesting that tap water samples may be held for up to 28

days prior to analysis.

Introduction

During a natural disaster, terrorist event, or accident affectingthe water sector, a large number of environmental samples willbe generated, likely overwhelming the capacity and capability ofany individual laboratory to provide sufficient analytical support.Tetramethylenedisulfotetramine (TETS) (CAS number 80-12-6),1–4

a rodenticide which has been the subject of several cases ofintentional and accidental poisonings,5–12 has been identied bythe EPA as an analyte of concern in drinking water matrixes forwhich analytical methods need to be developed (Fig. 1).13 Syno-nyms, along with physical and toxicological properties of TETS,are reviewed elsewhere.1–4 One synonym used for TETS is tetra-mine, which should not be confused with a biotoxin found in thesalivary glands of certain marine animals.14,15

Analytical procedures for the determination of TETS indifferent matrices have been reported primarily in clinicalsamples,16–19 for food,20–22 and in samples for forensicpurposes.18,22–25 Currently, there are no published methods forthe determination of TETS in the drinking water matrix. TETS iswater soluble1 enabling its accidental or intentional introduc-tion into drinking water and drinking water distributionsystems. The drinking water distribution system is frequently

aboratory Sciences, National Center for

e Control and Prevention, 4770 Buford

USA. E-mail: RJohnson6@cdc.gov

onal Homeland Security Research Center,

Cincinnati, OH 45268, USA

ceutical Sciences, College of Pharmacy1 Mercer University Drive, Atlanta, GA

784

investigated as a location for introduction of contaminants tooccur.26,27 Many drinking water distribution systems in theUnited States contain levels of residual oxidizing disinfectantssuch as chlorine or monochloramine to act as a barrier againstmicrobial regrowth. Such residual disinfectant may also deac-tivate susceptible chemicals; thus, it is important to understandthe reactivity of TETS with residual disinfectants.

A high throughput technique developed for analyzing TETSin urine specimens utilizing solid phase extraction for samplepreparation and isotope dilution for gas chromatography/massspectrometric quantitation16 was adapted for the analysis ofTETS in drinking water. This paper describes the adaptation ofthis method to the drinking water matrix and includes selectionof suitable preservatives and QA/QC approaches compatiblewith those used in many drinking water laboratories. Theselection of appropriate preservatives is needed to help ensurethe samples can be held at the receiving laboratory for a periodof time that will allow the laboratory to process the expectedbacklog of samples. Studies incorporating the selection ofappropriate preservatives will inherently provide insight intothe stability of TETS in the waters with residual disinfectants.

Fig. 1 Structure of tetramethylenedisulfotetramine.

This journal is © The Royal Society of Chemistry 2014

Technical Note Analytical Methods

Publ

ishe

d on

13

Mar

ch 2

014.

Dow

nloa

ded

by U

nive

rsity

of

Vic

tori

a on

27/

10/2

014

12:5

0:50

. View Article Online

ExperimentalChemical and standard materials

TETS and the corresponding 13C4-labeled internal standardwere purchased from Cambridge Isotope Laboratories (Cam-bridge, MA). High performance liquid chromatography (HPLC)-grade water, methanol, and acetonitrile were purchased fromTedia (Faireld, OH). The following sample preservationreagents were purchased from Sigma Aldrich (St. Louis, MO) atACS grade: ammonium chloride, sodium thiosulfate, sodiumsulte, L-ascorbic acid, ammonium acetate, citric acid, anddiazolidinyl urea (DU). Reagent grade sodium hypochlorite (5%solution), acetic acid, and sodium hydroxide were alsopurchased from Sigma Aldrich (St. Louis, MO). Research gradehelium (99.9999% pure) was used as a carrier gas for gaschromatography (Airgas, Atlanta, GA).

Instrumentation and consumables

Sample extraction was performed on a Caliper Life SciencesSciclone i1000 Liquid Handling Workstation (Hopkinton, MA)using a 60 mg 96-well Strata-X Polymeric sorbent plate (Phe-nomenex, Torrance, CA). Samples were prepared and collectedin 2 mL Nunc 96-well plates (Rochester, NY) with plastic lids(ThermoFisher Scientic, Waltham, MA) and all mixing stepswere performed using a plate shaker (ThermoFisher Scientic,Waltham, MA). Evaporation of samples was performed on aTurboVap 96 concentrator evaporator workstation (ZymarkCorporation, Hopkinton, MA). Extracted samples were trans-ferred to conical 300 mL autosampler vials (Lab Depot,Dawsonville, GA) for GC/MS analysis. Analytes were chromato-graphically separated on an Agilent 6890N gas chromatographtted with an Agilent HP-5MS 30 m � 0.25 mm inside diameter(i.d.) fused silica capillary (5%-phenyl)methylpolysiloxanecolumn coated with a 0.25 mm bonded lm (Santa Clara, CA).Mass spectrometry analysis was performed on an Agilent 5973mass spectrometer with electron ionization and ChemStationsoware (Santa Clara, CA).

Water sample preparation

Water samples were prepared in HPLC-grade water with theappropriate amounts of preservation agents and oxidants (i.e.hypochlorite andmonochloramine). Hypochlorite was preparedby dilution of 5% hypochlorite solution, as received. Mono-chloramine was created by mixing a 2.2 : 1 molar ratio ofammonium chloride : sodium hypochlorite. Measurements ofchlorine and monochloramine were made using Hach Color-imeter II Test Kits (Loveland, CO). Finished tap water samplesrepresenting a range of water quality parameters and disinfec-tion practices were supplied to EPA anonymously from vewater utilities throughout the United States.

Calibration and quality control material preparation

A primary stock solution of TETS was prepared by reconstituting20.6 mg of TETS into a total volume of 250 mL of acetonitrileusing a volumetric ask to yield a concentration of 82.4 mg L�1.

This journal is © The Royal Society of Chemistry 2014

Calibration solutions were prepared by diluting the primarystock solution with HPLC-grade water to concentrations of 0.5,1.0, 2.0, 10, 15, 25, 50, 100, and 250 ng mL�1. Pure HPLC-gradewater served as a blank. Two quality control (QC) pools werealso generated in HPLC-grade water at 5 mg L�1 (low-QC) and75 mg L�1 (high-QC). All calibration solutions, blanks, and QCswere stored at �70 �C until use and were brought to roomtemperature prior to extraction. An isotopically-labeled TETSinternal standard stock solution was prepared by reconstituting20.1 mg of 13C4-TETS into 200 mL acetonitrile using a volu-metric ask. This solution was further diluted to a workingstock concentration of 500 ng mL�1 in HPLC-grade water.

Sample extraction

TETS was extracted from calibration solutions, blanks, QCs, andwater samples by solid-phase extraction (SPE) using an auto-mated liquid handler. A 1000 mL aliquot of each was added toindividual wells of a 2 mL 96-well plate followed by the additionof a 50 mL aliquot of internal standard working solution to eachwell. Plates were mixed for 2 minutes on a plate shaker prior toextraction. The sample was loaded onto the wells of an SPE platepreconditioned with 1125 mL methanol followed by 1125 mLHPLC-grade water. The wells were then rinsed with 1125 mL of5% methanol in HPLC-grade water. Samples were eluted with800 mL of acetonitrile into a 2 mL 96-well plate, evaporated todryness under nitrogen gas at 65 �C, reconstituted in 100 mL ofacetonitrile, and transferred to autosampler vials for GC/MSanalysis.

GC/MS analysis

Analysis of extracts was performed as described.16 Briey, 1 mLof extract was injected into the GC at a constant ow of 1 mLmin�1 helium with an initial pressure of 10.5 PSI using anunpacked splitless liner with double taper at 250 �C. TETS wasseparated using the following column oven program: 100 �Cramped to 200 �C at 8 �C min�1, 200 �C ramped to 300 �C at50 �C min�1. The column was held at 300 �C for 1.7 min. Totalchromatography run time was 16.2 min. Mass spectrometricanalysis of TETS was also performed as previously described16

by single ion monitoring with a 100 ms dwell time. Native TETSmasses of 240 and 212 m/z were monitored as quantitation andconrmation ions, respectively, and isotopically-labeled TETSwas monitored at 244 m/z. ChemStation soware was used toacquire and process data. Analyte peaks were integrated at theretention time for TETS (11.6 minutes) which was conrmed bythe retention time of the isotopically-labeled internal standard.Calibration curves were generated by plotting the ratio of thenative analyte peak area to the internal standard peak areaagainst the expected concentration with 1/x weighting for eachcalibrator. The conrmation ratio, dened as the ratio of theconrmation ion peak area to the quantitation ion peak area,was determined for each calibration solution or in an analyticalbatch. For a peak to be identied as TETS, its conrmation ratiohad to be within 30% of the mean of the conrmation ratios ofthe calibration solutions. Statistical analysis was performedusing either Microso Excel 2010 (Microso Corporation,

Anal. Methods, 2014, 6, 2780–2784 | 2781

Table 1 Preservatives and dechlorinating agents investigated

CompoundConcentrationin sample (g L�1) Purpose

Ammonium chloride 0.1 Binds free chlorineAmmonium acetate 1.5 Binds free chlorineSodium thiosulfate 0.08 Dechlorinates free

chlorine and chloramineSodium sulte 0.05 Dechlorinates free

chlorine and chloramineAscorbic acid 0.1 Dechlorinates free

chlorine and chloramineCitric acid 9.3 pH adjustmentDiazolidinyl urea 1 Microbial inhibitor

Analytical Methods Technical Note

Publ

ishe

d on

13

Mar

ch 2

014.

Dow

nloa

ded

by U

nive

rsity

of

Vic

tori

a on

27/

10/2

014

12:5

0:50

. View Article Online

Redmond, WA) or SAS statistical soware (SAS Institute, Inc.,Cary, NC).

Storage stability studies

The stability of TETS in HPLC-grade water buffered to pH 8,chlorinated water (3 mg L�1 free chlorine), and mono-chloraminated water (2 mg L�1 monochloramine) was investi-gated in the presence of the preservatives and dechlorinatingagents listed in Table 1 at pH 8.0. The purpose for each preser-vative's use and the preservative concentrations tested are alsolisted in Table 1. The samples for the storage stability studieswere fortied with 75 mg L�1 of TETS and held in sealed 96-wellplates at either 4 �C or 25 �C in the dark. Aliquots of sample typewere extracted and analyzed, as described above, immediatelyfollowing preparation (day 0) and on days 7, 14, and 28.

Results and discussionMethod performance

Measurement of TETS in HPLC-grade water was characterizedover the course of 20 analytical batches determined over 10days. An analytical batch consisted of calibration solutions, twoquality control samples (high and low concentrations), blanks,and up to 20 unknown samples. The mean measured accuracyfor all standards was within 6% of the actual concentration andanalyte response was linear over the entire calibration rangewith a coefficient of linearity, R2, of 0.999. The mean measuredconcentration for the lowest standard, 0.5 mg L�1, was 0.48 �0.06 mg L�1. Two quality control samples consisting of TETS inHPLC-grade water at 5 mg L�1 (low-QC) and 75 mg L�1 (high-QC)were measured in each analytical batch (Table 2). An analyticalbatch contained up to 20 water samples in addition to the QCsamples. The accuracy of the mean was 100 and 101% for low-

Table 2 Precision and accuracy of analysis (n ¼ 20) of TETS QC poolsanalyzed over 10 days

QC poolConcentration(mg L�1)

Mean of 20replicates (mg L�1) RSD (%)

Accuracy(%)

Low-QC 5.0 5.03 5.6 100High-QC 75 75.5 3.7 101

2782 | Anal. Methods, 2014, 6, 2780–2784

and high-QCs, respectively. Analytical precision of the qualitycontrol pools was 5.6 and 3.7% for the low-QC and high-QC,respectively. Because precision and accuracy characterized forthis method fall within 10%, this method is classied as a highprecision and accuracy ultra-trace method according to Taylormethod classication.28

The lower limit of detectability of TETS was estimated in twoways. First, the limit of detection (LOD) for TETS in HPLC-gradewater was calculated. To calculate this LOD, the standarddeviation of the lowest three calibration solutions were plottedagainst their respective concentration and the y-intercept of theresulting line was multiplied by three.28 Using this method theLOD for TETS was calculated as 0.110 mg L�1. The second esti-mation was based on the procedure discussed at 40 CFR,29 asthe minimum concentration of a substance that can bemeasured and reported with 99% condence that the analyteconcentration is greater than zero and is determined fromanalysis of a sample in a given matrix containing the analyte.The method detection limit (MDL) is calculated under 40 CFRPart 136 as follows:

MDL ¼ s � t(n�1,1�a¼0.99)

where s ¼ standard deviation of replicate analyses,t(n�1,1�a¼0.99) ¼ Student's t value for the 99% condence levelwith n � 1 degrees of freedom, and n ¼ number of replicates.Based on twenty replicate analysis of a 0.50 mg L�1 standard, thecalculated MDL was 0.15 mg L�1. The calculated MDL for the95% condence level was 0.11 mg L�1.

In practice, however, the minimum reportable level (MRL) isthe concentration of the lowest standard, 0.5 mg L�1. Likewise,the highest reportable level is the concentration of the highestcalibrator, 250 mg L�1, for this method.

Stability study of TETS in preserved chlorinated andmonochloraminated water samples

The stability of TETS in the presence of preserved and unpre-served chlorinated and monochloraminated water was investi-gated as a function of time. Chlorinated water (3 mg L�1 freechlorine), monochloraminated water (2 mg L�1 monochlor-amine), and HPLC-grade water buffered to pH 8.0 were gener-ated to simulate a wide range of drinking water samples. TETSwas added into each water type at a concentration of 75 mg L�1,along with the preservatives listed in Table 1, and stored ateither 4 �C or 25 �C to simulate refrigerated or room tempera-ture storage conditions. Blank samples consisting of each watertype without TETS were included in the analysis and were free ofanalyte in all cases. No degradation of TETS was observed in anyof the unpreserved water types (Table 3). The addition ofpreservatives, which may be required in some specicinstances, to each water type and storage temperature did notsignicantly inuence the amount of TETSmeasured. TETS wasfound to be stable across the 28 days of this study and isconsistent with other stability ndings.10,16,21 The stability ofTETS even in the presence of theses levels of chlorinationindicates that water source contamination with TETS can pose along-term hazard. Secondary and tertiary poisonings by food

This journal is © The Royal Society of Chemistry 2014

Table 3 Percentage of TETS measured in HPLC grade water fortified with 75 mg L�1 TETS and various preservatives, oxidants, and dechlorinatingagentsa

Water type Preservative/dechlorinating agent

Day 0 Day 7 Day 14 Day 28

4 �C 25 �C 4 �C 25 �C 4 �C 25 �C 4 �C 25 �C

Deionized — 109 � 3 102 � 6 110 � 10 112 � 4 101 � 2 103 � 2 107 � 4 108 � 4Chlorine — 104 � 7 105 � 5 107 � 9 111 � 5 102 � 1 105 � 2 113 � 4 118 � 2Monochloramine — 108 � 7 101 � 9 100 � 2 108 � 4 101 � 4 104 � 1 110 � 4 110 � 10Chlorine Ammonium chloride 106 � 7 106 � 5 104 � 5 113 � 8 116 � 4 103 � 1 124 � 6 112 � 5Chlorine Sodium thiosulfate 107 � 7 99 � 3 96 � 2 111 � 5 100 � 2 96 � 2 111 � 4 115 � 9Monochloramine Sodium thiosulfate 109 � 9 103 � 4 99 � 6 111 � 5 113 � 2 102 � 2 115 � 2 113 � 4Chlorine Sodium sulte 110 � 20 105 � 5 110 � 6 105 � 5 101 � 2 105 � 1 111 � 4 110 � 10Chlorine Ascorbic acid 110 � 10 103 � 6 101 � 7 110 � 10 104 � 3 114 � 3 110 � 10 111 � 4Chlorine Ammonium acetate 101 � 8 99 � 0 116 � 6 111 � 3 114 � 2 106 � 3 107 � 2 110 � 3Deionized Citric acid 109 � 8 108 � 6 104 � 1 110 � 5 95 � 2 112 � 4 114 � 4 110 � 2Deionized Diazolidinyl urea 100 � 30 96 � 5 102 � 6 103 � 2 99 � 1 100 � 10 109 � 8 110 � 6

a The percentage of TETS is reported (as x � sn�1 with n ¼ 3) for the days and temperatures indicated.

Table 4 Percentage of TETS measured in several tap water matrices fortified with 75 mg L�1 TETS.a Water quality parameters and the residualdisinfectants used in the tap waters are indicated in the footnotes

Water type

Day 0 Day 7 Day 14 Day 28

4 �C 25 �C 4 �C 25 �C 4 �C 25 �C 4 �C 25 �C

Ground water 1b (chlorine) 103 � 8 109 � 3 105 � 3 113 � 4 113 � 4 104 � 5 122 � 2 114 � 7Surface water 2c (monochloramine) 107 � 8 100 � 1 99 � 3 114 � 3 92 � 3 105 � 6 119 � 6 111 � 3Surface water 3d (chlorine) 110 � 3 96.8 � 0.3 102 � 3 106 � 6 108 � 6 107 � 5 111 � 2 107 � 2Surface water 4e (monochloramine) 102 � 2 94 � 4 102 � 1 107 � 3 98 � 7 98 � 5 109 � 2 114 � 3Surface water 5f (chlorine) 102 � 3 99 � 7 117 � 4 108 � 3 108 � 6 108 � 6 112 � 3 116 � 8

a The percentage of TETS is reported (as x � sn�1 with n ¼ 3) for the days and temperatures indicated. b Total organic carbon (TOC) not detected inwell-eld via EPA method 524.3 or equivalent; pH 7.6; hardness 350 mg L�1; chlorine 0.2–0.4 mg L�1; (monthly averages). c TOC 7.6 mg L�1; pH 9.2;hardness 65 mg L�1; monochloramines 2.4 mg L�1 (monthly averages). d TOC 2.0 mg L�1; pH 7.3; hardness 135 mg L�1; chlorine 1 mg L�1 (monthlyaverages). e TOC 2.3 mg L�1; pH 7.4; hardness 190 mg L�1; monochloramine 3.4 mg L�1 (monthly averages). f TOC 1.0 mg L�1; pH 8.5; hardness 130mg L�1; chlorine 0.8 mg L�1 (monthly averages).

Technical Note Analytical Methods

Publ

ishe

d on

13

Mar

ch 2

014.

Dow

nloa

ded

by U

nive

rsity

of

Vic

tori

a on

27/

10/2

014

12:5

0:50

. View Article Online

chain consumption are possible,10 increasing this hazard inareas where contaminated water sources are used in food orbeverage preparation or may be consumed by livestock andother animals.

Stability and determination of TETS in tap water samples

Five tap water samples were collected from various locationsaround the United States representing wide ranges of totalorganic content (TOC), hardness, and pH, as indicated in Table4. Of these tap water samples, two contained monochloramineand three contained chlorine as a secondary disinfectant. Thesecondary disinfectant serves to prevent microbial growth, butits efficacy for chemical removal is contaminant specic.9

TETS was added into pools of each tap water to a concen-tration of 75 mg L�1 and samples were held up to 28 days ateither 4 �C or 25 �C to simulate refrigerated and roomtemperature conditions, respectively. No preservative wasadded into any tap water sample based on the previous studywhich indicated that TETS is stable in the presence of chlorineand monochloramine up to at least 28 days. As was observedpreviously, TETS remained stable in all water types and

This journal is © The Royal Society of Chemistry 2014

temperature conditions tested through the entire 28 dayholding study, indicating that substances in these tap watersamples do not interfere with the analysis (Table 4). Theamount of TETS measured, expressed as a percentage of theamount fortied into the tap water sample, averaged 100 � 3%initially and 112 � 13% aer being held for 28 days, which isstatistically indistinguishable at the 95% condence level. Thehigher variability at 28 days may be an experimental artifact, butmay reect variable changes in sample composition amongstthe water types studied.

Conclusions

The temporal stability of TETS in the presence of disinfectantsand in actual drinking water samples suggests that remediationof water contaminated with TETS may be necessary, and suit-able detection methods are necessary to protect these watersources. To compare the analytical performance for TETSdetermination to the toxicology of TETS, it is useful to considerthat the estimated human oral LD50 dose for TETS is 0.1 to0.3 mg kg�1 and 7–10mg is adequate to kill an adult.6 Assumingthis amount is ingested over the course of a day, and a daily

Anal. Methods, 2014, 6, 2780–2784 | 2783

Analytical Methods Technical Note

Publ

ishe

d on

13

Mar

ch 2

014.

Dow

nloa

ded

by U

nive

rsity

of

Vic

tori

a on

27/

10/2

014

12:5

0:50

. View Article Online

consumption of water of 2 L a day,30 this corresponds to aconcentration of 3.5–5mg L�1. While the dose response curve ofTETS is unknown, the MRL is 3–4 orders of magnitude lowerthan this concentration. While remediation goals are inherentlysite specic, the MRL suggests the applicability of this methodduring water contamination incidents involving TETS. Impor-tantly, for a wide scale contamination incident in whichhundreds or thousands of samples may be generated, the use ofautomated liquid handling and high throughput formattingfacilitates the simultaneous extraction of a large number of watersamples with minimal effort while reducing the potential fortechnical errors. Also of importance is the use of isotope dilutionfor quantication to increase the likelihood that the method maybe applied across many sample types; although suitable proce-dural quality control measures should be employed in theunlikely instance that an interfering substance is present and notaccounted for by isotope dilution. For example, it may benecessary to monitor 216 m/z from the isotopically labeled TETSin the unlikely event that an interferent with the primary TETSion (244 m/z) is unusable, although this was not observed in anyof the drinking water samples analyzed in this study or in clinicalsamples previously reported.16

Acknowledgements

The authors would like to thank Benjamin Ku for assisting withgraphical editing. The research described herein has been peerand administratively reviewed and has been approved forpublication as a joint U.S. Environmental Protection Agency(EPA) and Centers for Disease Control and Prevention (CDC)document. The USEPA, through its Office of Research andDevelopment, funded and collaborated with the CDC in theresearch described herein under EPA IA# DW75-92259701. Notethat approval does not signify that the contents necessarilyreect the views of the USEPA, the CDC, the Public HealthService, or the US Department of Health and Human Services.Reference herein to any specic commercial product, process,or service by trade name, trademark, manufacturer, or other-wise does not necessarily constitute or imply its endorsement,recommendation, or favoring by the United States government.The views and opinions expressed herein do not necessarilystate or reect those of the United States government and shallnot be used for advertising or product endorsement purposes.

Notes and references

1 INCHEM, Tetramethylene Disulfotetramine, http://www.inchem.org/documents/pims/chemical/pim982.htm,accessed September 2013, 2002.

2 A.R.Haskell andE. Voss, J. Am. Pharm. Assoc., 1957, 46, 239–242.3 X. Deng, G. Li, R. Mei and S. Sun, Clin. Toxicol., 2012, 50,172–175.

4 L. Bohlin, J. Ethnopharmacol., 1993, 38, 215–223.5 CDC, Morbidity and Mortality Weekly Report, 2003, vol. 52,pp. 199–201.

6 K. S. Whitlow, M. Belson, F. Barrueto, L. Nelson andA. K. Henderson, Ann. Emerg. Med., 2005, 45, 609–613.

2784 | Anal. Methods, 2014, 6, 2780–2784

7 L. Zhou, L. Liu, L. Chang and L. Li, J. Forensic Sci., 2011, 56,S234–S237.

8 Y. Zhang, M. Su and D.-P. Tian, Forensic Sci. Int., 2011, 204,E24–E27.

9 A. S. Khan, D. L. Swerdlow and D. D. Juranek, Public HealthRep., 2001, 116, 3–14.

10 E. Croddy, Arch. Toxicol., 2004, 78, 1–6.11 F. Barrueto, P. M. Furdyna, R. S. Hoffman, R. J. Hoffman and

L. S. Nelson, J. Toxicol., Clin. Toxicol., 2003, 41, 991–994.12 F. Barrueto Jr, L. S. Nelson, R. S. Hoffman, M. B. Heller,

P. M. Furdyna, R. J. Hoffman, K. S. Whitlow, M. G. Belsonand A. K. Henderson, JAMA, J. Am. Med. Assoc., 2003, 289,2640–2642.

13 USEPA, Selected Analytical Methods (SAM) for EnvironmentalRemediation and Recovery – 2012, http://www.epa.gov/sam/,accessed September 2013, 2012.

14 U. Anthoni, L. Bohlin, C. Larsen, P. Nielsen, N. H. Nielsenand C. Christophersen, Toxicon, 1989, 27, 707–716.

15 A. J. Power, B. F. Keegan and K. Nolan, Toxicon, 2002, 40,419–425.

16 E. Hamelin, L. Swaim, J. Thomas, R. Kobelski andR. C. Johnson, J. Chromatogr. B: Anal. Technol. Biomed. LifeSci., 2010, 878, 2541–2547.

17 J. T. Liu, C. C. Fan and G. H. Wu, Clin. Chem., 1993, 39, 173–174.

18 J. T. Liu, C. C. Fan, G. H. Wu and H. Meiyi, J. Forensic Sci.,1993, 38, 236–238.

19 T. G. Luan, G. K. Li, M. Q. Zhao and Z. X. Zhang, Anal. Chim.Acta, 2000, 404, 329–334.

20 L. S. De Jager, G. A. Perfetti and G. W. Diachenko, J. Sep. Sci.,2009, 32, 1081–1086.

21 J. Owens, S. Hok, A. Alcaraz and C. Koester, J. Agric. FoodChem., 2009, 57, 4058–4067.

22 G. H. Wu and M. Y. Huang, J. Forensic Sci., 1992, 37, 1213–1215.

23 C. G. Fraga, G. A. P. Acosta, M. D. Crenshaw, K. Wallace,G. M. Mong and H. A. Colburn, Anal. Chem., 2011, 83,9564–9572.

24 C. G. Fraga, J. H. Wahl and S. P. Nunez, Forensic Sci. Int.,2011, 210, 164–169.

25 D. Zeng, B. Chen, S. Yao and J. Ying, Forensic Sci. Int., 2006,159, 168–174.

26 USEPA, Securing and Sustaining Water Systems Research,http://www.epa.gov/nhsrc/aboutwater.html, accessedSeptember 2013, 2012.

27 USEPA, Water Security Initiative, http://water.epa.gov/infrastructure/watersecurity/lawsregs/initiative.cfm, accessedSeptember 2013, 2012.

28 J. K. Taylor, Quality Assurance of Chemical Measurements,CRC-Press, Boca Raton, Florida, October 2 1987.

29 CFR, PART 136—Guidelines establishing test proceduresfor the analysis of pollutants, http://www.ecfr.gov/cgi-bin/text-idx?c¼ecfr&SID¼b51546c3242bb93ebbc491e6f136304c&rgn¼div5&view¼text&node¼40:24.0.1.1.1&idno¼40, accessedSeptember 2013, 2013.

30 USEPA, Exposure Factors Handbook, http://www.epa.gov/ncea/e/report.html, accessed September 2013, 2011.

This journal is © The Royal Society of Chemistry 2014