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METHOD 557: DETERMINATION OF HALOACETIC ACIDS,
BROMATE, AND DALAPON IN DRINKING WATER BY ION
CHROMATOGRAPHY ELECTROSPRAY IONIZATION
TANDEM MASS SPECTROMETRY (IC-ESI-MS/MS)
                     . jjj-zidanitu&h Env'umnm
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METHOD 557     DETERMINATION OF HALOACETIC ACIDS, BROMATE, AND
                 DALAPON IN DRINKING WATER BY ION CHROMATOGRAPHY
                 ELECTROSPRAY IONIZATION TANDEM MASS SPECTROMETRY
                 (IC-ESI-MS/MS)
                                   Version 1.0
                                 September 2009
               A. D. Zaffiro and M. Zimmerman (Shaw Environmental, Inc.)
                     B. V. Pepich (U.S. EPA, Region 10 Laboratory)
       Rosanne W. Slingsby, R. F. Jack and Christopher A. Pohl (Dionex Corporation)
           D. J. Munch (U.S. EPA, Office of Ground Water and Drinking Water)
                         TECHNICAL SUPPORT CENTER
               OFFICE OF GROUND WATER AND DRINKING WATER
                  U. S. ENVIRONMENTAL PROTECTION AGENCY
                            CINCINNATI, OHIO 45268
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                                       METHOD 557

 DETERMINATION OF HALOACETIC ACIDS, BROMATE, AND DALAPON IN DRINKING
 WATER BY ION CHROMATOGRAPHY ELECTROSPRAY IONIZATION TANDEM MASS
                            SPECTROMETRY (IC-ESI-MS/MS)

1.    SCOPE AND APPLICATION

   1.1   Method 557 is a direct-inject, ion chromatography, negative-ion electrospray ionization,
         tandem mass spectrometry (IC-ESI-MS/MS) method for the determination of haloacetic acids
         in finished drinking water. Bromate and dalapon (2,2-dichloropropionic acid) may be
         measured concurrently with the haloacetic acids. Real time, chromatographic separation of
         common anions in drinking water (matrix elimination) is a key feature of this method.
         Acceptable method performance has been demonstrated for matrix ion concentrations of 320
         mg/L chloride,  250 mg/L sulfate, 150 mg/L bicarbonate and 20 mg/L nitrate. Method 557
         requires the use of MS/MS in Multiple Reaction Monitoring (MRM) mode to enhance
         selectivity. Precision and accuracy data have been generated for the detection of nine
         haloacetic acids, bromate, and dalapon in reagent water, synthetic sample matrix, and finished
         drinking water from both ground water and surface water sources.  The single laboratory
         Lowest Concentration Minimum Reporting Level (LCMRL) has also been determined in
         reagent water. Method 557 is applicable for the measurement of the following analytes:

                                                   Chemical Abstracts Services
                          Analvte                  Registry Number (CASRN)
                     Bromate (BrO3")                 15541-45-4 (BrO3" anion)
              Bromochloroacetic acid (BCAA)                 5589-96-8
             Bromodichloroacetic acid (BDCAA)              71133-14-7
             Chlorodibromoacetic acid (CDBAA)               5278-95-5
                          Dalapon                            75-99-0
                Dibromoacetic acid (DBAA)                   631-64-1
                Dichloroacetic acid (DCAA)                    79-43-6
              Monobromoacetic acid (MBAA)                  79-08-3
              Monochloroacetic acid (MCAA)                  79-11-8
                Tribromoacetic  acid (TBAA)                    75-96-7
                Trichloroacetic  acid (TCAA)                    76-03-9

   1.2   The chromatographic and MRM mass spectrometry conditions described in this method were
         developed using commercially available IC-ESI-MS/MS systems.

   1.3   The single laboratory LCMRL is the lowest spiking concentration such that the probability of
         spike recovery in the 50% to 150% range is at least 99%. Single laboratory LCMRLs for the
         analytes in this  method ranged from 0.042 to 0.58 microgram per liter (|lg/L),  and are listed in
         Table 5. The procedure  used to determine the LCMRL is described elsewhere.1


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    1.4   Laboratories using this method are not required to determine LCMRLs, but they must
         demonstrate that the Minimum Reporting Level (MRL) for each analyte meets the
         requirements described in Section 9.2.4.

    1.5   Detection Limit (DL) is defined as the statistically calculated minimum concentration that can
         be measured with 99% confidence that the reported value is greater than zero.2  The DL is
         dependent on sample matrix, fortification concentration, and instrument performance.
         Determining the  DL for analytes in this method is optional (Sect. 9.2.6). DLs for method
         analytes fortified into reagent water ranged from 0.015 to 0.20 jig/L (Table 6).

    1.6   This method is intended for use by analysts skilled in the operation of IC-ESI-MS/MS instru-
         mentation and the interpretation of the associated data.

    1.7   METHOD FLEXIBILITY -  The  laboratory is permitted to select 1C columns, eluent
         compositions, eluent suppression  techniques, and ESI-MS/MS conditions different from those
         utilized to develop the method. However, the basic chromatographic elements of the method
         must be retained. In order to avoid the effects of matrix suppression, the method analytes
         must be substantially resolved chromatographically from common anions in drinking water.
         Samples must be analyzed by direct injection. Filtering and pretreatment by use of solid
         phase extraction  are not permitted. At a minimum, the four internal standards prescribed in
         this method must be used  Changes may not be made to sample collection and
         preservation (Sect. 8) or to the quality control (QC) requirements (Sect. 9)   Method
         modifications should be considered only to improve method performance.  Modifications that
         are introduced in the interest of reducing cost or sample processing time, but result in poorer
         method performance, may not be  used. In all cases where method modifications are proposed,
         the analyst must  perform the procedures outlined in the Initial Demonstration of Capability
         (IDC, Sect. 9.2),  verify that all  QC acceptance criteria in  this method (Tables 11 and 12) are
         met, and verify method performance in a real sample matrix (Sect. 9.4).

         NOTE: Single quadrupole instruments are not permitted.

2.   SUMMARY OF METHOD

     Residual  chlorine present in drinking water samples is reacted with ammonium chloride to form
     chloramines, effectively preventing chlorine-mediated formation of method  analytes during
     storage. In addition, the combined chlorine residual prevents  microbial degradation in the sample.
     Prior to analysis, isotopically enriched analytes (monochloroacetic acid-2-13C, monobromoacetic
     acid-7-13C, dichloroacetic acid-2-13C,  and trichloroacetic acid-2-13C) are added to the samples as
     internal standards. An aliquot of the sample is injected without cleanup or concentration onto an
     ion exchange column specifically designed to separate method analytes from the following
     common  anions (matrix components) in drinking water:  chloride, carbonate, sulfate, and nitrate.
     The matrix components in the column eluate are monitored via conductivity detection and then
     diverted to waste; the analytes of interest are directed into the ESI-MS/MS system. Acetonitrile is
     added post-column to enhance desolvation of the method analytes in the ESI interface.  Each
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     method analyte is qualitatively identified via a unique mass transition, and the concentration is
     calculated using the integrated peak area and the internal standard technique.

3.    DEFINITIONS

   3.1    ANALYSIS BATCH - A sequence of samples, analyzed within a 30-hour period, including
          no more than 20 field samples. Each Analysis Batch must also include all required QC
          samples, which do not contribute to the maximum field sample total of 20. The required QC
          samples include:

             Laboratory Reagent Blank (LRB),
             Continuing Calibration Check (CCC) Standards,
             Laboratory Fortified Sample Matrix (LFSM), and
             Laboratory Fortified Sample Matrix Duplicate or Laboratory Duplicate (LFSMD or LD).

   3.2    CALTERATION STANDARD - An aqueous solution of the method analytes prepared from
          the Primary Dilution Standard (Sect.  3.21) solution. The calibration standards are used to
          calibrate the instrument response with respect to analyte concentration.

   3.3    CONTINUING CALIBRATION CHECK - A calibration standard containing the method
          analytes and internal standards, which is analyzed periodically to verify the accuracy of the
          existing calibration.

   3.4    DETECTION LIMIT (DL) - The minimum concentration of an analyte that can be
          identified, measured, and reported with 99% confidence that the analyte concentration is
          greater than zero. This is a statistical determination (Sect. 9.2.6), and accurate quantitation is
          not expected at this level.

   3.5    DIVERT WINDOW - The period of time during which the column eluate is directed to
          waste for the purpose of diverting matrix components away from the ESI-MS/MS system.

   3.6    ELUTION WINDOW - The period of time during which the column eluate is directed to the
          ESI-MS/MS system for the purpose of measuring the method analytes.

   3.7    INTERNAL STANDARD - A pure compound added to all standard solutions and samples
          in a known amount.  Each internal standard is assigned to a specific analyte or multiple
          analytes, and is used to measure relative response.

   3.8    ION SUPPRESSION/ENHANCEMENT - An observable loss or increase in analyte
          response in complex (field) samples as compared to the response obtained in standard
          solutions.

   3.9    LABORATORY DUPLICATES (LDs) - Two sample aliquots (LDi  and LD2) taken in the
          laboratory from a single sample bottle, and analyzed separately with identical procedures.
          By cancelling variation contributed from sample collection, preservation, and storage
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      procedures, Laboratory Duplicates provide an estimate of precision associated specifically
      with the analytical determination.

3.10  LABORATORY FORTIFIED BLANK (LFB) - An aliquot of reagent water, containing the
      method preservative, to which known quantities of the method analytes are added. The LFB
      is used during the IDC to verify method performance for precision and accuracy.

3.11  LABORATORY FORTIFIED SAMPLE MATRIX (LFSM) - An aliquot of a field sample to
      which known quantities of the method analytes are added. The LFSM is processed and
      analyzed as a sample, and its purpose is to determine whether the sample matrix contributes
      bias to the analytical results.

3.12  LABORATORY FORTIFIED SAMPLE MATRIX DUPLICATE (LFSMD) - A second
      aliquot of the field sample used to prepare the LFSM which is fortified and analyzed
      identically to the LFSM. The LFSMD is used instead of the Laboratory Duplicate to assess
      method precision when the method analytes are rarely found at concentrations greater than
      the MRL.

3.13  LABORATORY FORTIFIED SYNTHETIC SAMPLE MATRIX (LF S SM) - Aliquots of the
      Laboratory Synthetic Sample Matrix (Sect. 3.15) fortified with known quantities of the
      method analytes. The LFSSM is analyzed at the beginning of each Analysis Batch to verify
      that the matrix components elute within the divert windows, and to ensure that no portion of
      an analyte peak is inadvertently diverted to waste. The LFSSM also serves as a QC sample
      for the purpose of estimating precision and accuracy during the IDC.

3.14  LABORATORY REAGENT BLANK (LRB) - An aliquot of reagent water that contains the
      preservative and internal standards. The LRB is used to determine if the method analytes or
      other interferences are introduced from the laboratory environment, the reagents or
      glassware, and to test for cross contamination.

3.15  LABORATORY SYNTHETIC SAMPLE MATRIX (LSSM) - For this  method, the LSSM is
      a solution of common anions prepared at high concentrations relative to  their typical
      occurrence in drinking water. Guidance for preparation of the LSSM  is  provided  in Section
      7.2.

3.16  LOWEST CONCENTRATION MINIMUM REPORTING LEVEL (LCMRL) - The single
      laboratory LCMRL is the lowest spiking concentration such that the probability of spike
      recovery in the 50% to 150% range is at least 99%l

3.17  MATERIAL SAFETY DATA SHEETS (MSDS) - Written information provided by vendors
      concerning a chemical's toxicity, health hazards, physical properties, fire and reactivity data,
      storage instructions, spill response procedures, and handling precautions.

3.18  MINIMUM REPORTING LEVEL (MRL) - The minimum concentration that can be
      reported by a laboratory as a quantified value for the method analyte in a sample following
      analysis.  This concentration must meet the criteria defined in Section 9.2.4 and must be no
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          lower than the concentration of the lowest calibration standard for each method analyte.  A
          laboratory may be required to demonstrate a specific MRL by a regulatory body if this
          method is being performed for compliance purposes.

   3.19   MULTIPLE REACTION MONITORING (MRM) - A mass spectrometric technique in
          which a precursor ion (Sect. 3.20) is first isolated, then subsequently fragmented into a
          product ion(s) (Sect. 3.23). Quantitation is accomplished by monitoring a specific product
          ion. As described in Section 10.2.2, MS parameters must be optimized for each precursor
          ion and product ion.

   3.20   PRECURSOR ION - The precursor ion is the gas-phase species corresponding to the method
          analyte produced in the ESI interface. In MS/MS, the precursor ion is mass selected and
          fragmented by collision-activated dissociation to produce distinctive product ions  of smaller
          mass/charge (m/z) ratio.

   3.21   PRIMARY DILUTION STANDARD (PDS) - An aqueous solution containing the method
          analytes (or internal standards) prepared from Stock Standard Solutions and diluted as
          needed to prepare calibration standards and sample fortification solutions.

   3.22   PROCEDURAL CALIBRATION - A calibration technique in which calibration standards
          are processed through the entire method, including sample preparation and addition of
          preservatives.

   3.23   PRODUCT-ION - For the purpose of this method, a product ion is one of the fragment ions
          produced in MS/MS by collision-activated dissociation of the precursor ion.

   3.24   QUALITY CONTROL SAMPLE (QCS) - A solution containing the method analytes at a
          known concentration, which is obtained from a source external to the laboratory and different
          from the source of calibration standards. The purpose of the QCS is to verify the accuracy of
          the primary calibration standards.

   3.25   REAGENT WATER - Purified water that does not contain any measurable quantity of the
          method analytes or interfering compounds at or above 1/3  the MRL.

   3.26   STOCK STANDARD SOLUTION (SSS) - A concentrated solution containing one or more
          of the method analytes that is prepared in the laboratory using assayed reference materials or
          purchased  from a reputable commercial  source, so that the concentration and purity of
          analytes are traceable to certificates of analysis.

4.    INTERFERENCES

   4.1    GLASSWARE - During method development, no problems with stability of the method
          analytes, interferences, or cross contamination related to glass containers were observed.
          Sample collection bottles and vials containing samples and standards may be reused after
          thorough rinsing with reagent water. Dry glassware in an oven or air dry. Teflon-faced
          septa, if not punctured, may be cleaned and reused. Vials containing PDS solutions must be
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       rinsed with methanol before reuse and the septa discarded. It is recommended that
       autosampler vials and septa be discarded after a single use.

4.2    REAGENTS AND EQUIPMENT - Method interferences may be caused by contaminants in
       solvents and reagents (including reagent water).  All laboratory reagents must be routinely
       demonstrated to be free from interferences (less than 1/3 the MRL for the method analytes)
       under the conditions of the analysis. This may be accomplished by analyzing LRBs as
       described in Section 9.3.1.

4.3    MATRIX INTERFERENCES - Matrix interferences are caused by contaminants that are
       present in the sample. The extent of matrix interferences will vary considerably from source
       to source depending upon the nature of the water. Matrix components may directly interfere
       by producing a signal at or near the retention time of an analyte peak. Matrix components
       may also suppress or enhance the signal of the method analytes.  (Suppression and
       enhancement effects occur during the ionization process in the electrospray source when a
       co-eluting contaminant influences the ionization of the analyte of interest.) Common anions
       present in drinking water matrices, which would cause matrix suppression, are diverted from
       the MS. In addition, the internal standards recommended in this method performed well in a
       variety  of matrices.  However, these measures may not compensate for all potential matrix
       effects.  The analysis of Laboratory Fortified Sample Matrix (Sect. 9.3.5) provides evidence
       for the presence (or absence) of matrix effects.

4.4    INTERFERENCE FROM SYSTEM CONTAMINANTS - Contaminants in the mobile
       phase, autosampler, column, or other system components may produce a signal at or near the
       retention time of a method analyte.  Such an interfering signal may be observed as a shoulder
       on an analyte peak or detected as an analyte peak in the Laboratory Reagent Blank. If this
       occurs,  attempt to eliminate the interference.  If unsuccessful, investigate alternate MRM
       transitions.

4.5    INTERFERENCE FROM INTERNAL STANDARDS - Depending on the source and
       purity, labeled haloacetic acid internal standards may contain a small percentage of the
       corresponding native analyte. Usually, such contributions are insignificant when performing
       the method within the normal calibration range of 0.25 to 20 |lg/L.  However, the
       contribution may be significant when attempting to determine LCMRLs and DLs.  The
       labeled internal standards must meet the purity requirements stated in the IDC (Section
       9.2.1).

4.6    BREAKDOWN OF DALAPON, CDBAA, AND TBAA IN AQUEOUS MEDIA - Under
       the conditions described in Section 8, the method analytes are stable in aqueous media within
       the stated holding time. However, during method development, dalapon, CDBAA, and
       TBAA—in both standards and drinking water samples—degraded while awaiting analysis in
       conventional autosamplers that may reach temperatures between 25°  and 30 °C during
       operation. For this reason, refrigerated autosamplers, capable of maintaining samples at a
       temperature of less than or equal to 10 °C, are required for use with Method 557.
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4.7    ION SUPPRESSION IN THE PRESENCE OF CHLORITE - The chlorite anion (C1O2") may
       be present in drinking water distribution systems employing chlorine dioxide (C1O2) as a
       disinfectant. During method development studies, severe signal suppression of MCAA and
       excessive band broadening of the MCAA chromatographic peak profile were observed in the
       presence of 1 mg/L C1O2", the maximum contaminant level (MCL).  As depicted in Figure 4,
       the C1O2" anion co-eluted with MCAA.  Method 557 is not applicable to drinking water
       treated with C1O2 unless the laboratory demonstrates alternate chromatographic conditions
       (other than those used to develop the method, Section 17, Table 1) that eliminate the
       suppression. That is, chlorite must be resolved chromatographically from MCAA and the
       other method analytes.  Alternately, the laboratory must demonstrate that the chlorite anion is
       not present in the sample matrix.

4.8    SIGNAL SUPPRESSION DUE TO EXCESSIVE BACKGROUND CONDUCTIVITY -
       The ESI interface is sensitive to the background conductivity  of column eluate.  The analyst
       should observe the background conductivity prior to starting an analysis sequence each day.
       If using a concentration gradient, make this observation at the initial eluent concentration. At
       the maximum concentration in the gradient, the background conductivity will increase
       compared to the conductivity at the initial concentration. In this region of the chromatogram,
       the potential for suppression from the background conductivity is greatest. Such suppression
       may be evidenced by difficulty detecting TBAA, or by peak areas that are low compared to
       historical values when the background conductivity was lower. Section 11.3.2 provides
       guidance on corrective action if background conductivity is problematic.

4.9    PEAK TAILING - Peak tailing may be observed as the column ages. Peak tailing will limit
       the analyst's ability to separate matrix components from the method analytes. Peak tailing
       should be minimal with a properly  configured ion chromatography system when using a new
       column. (See Figure 2.) If tailing is observed with continued column use, original
       performance can usually be restored by  replacing the guard column.

4.10   EFFECT OF TEMPERATURE ON ANALYTE STABILITY - MBAA CDBAA, and TBAA
       degrade readily in aqueous eluent at high pH. Such conditions may exist in the mobile phase
       of ion exchange columns. The reaction is temperature dependent. For this reason, the
       separation is performed at subambient temperature, specifically 15 °C. At 15 °C,
       degradation in the column eluent is minimized.

4.11   MANAGING DIVERT WINDOWS - Analyte retention times may slowly shift toward
       lower values as the column ages or becomes fouled. Because this method employs multiple
       divert windows, the analyst must monitor peak locations on a daily basis to ensure that each
       analyte peak elutes entirely within the MS/MS elution windows.  Guidance for verifying
       elution/divert windows is provided in Section 10.2.5. To avoid loss  of column capacity,
       follow the manufacturer's instructions for proper operating temperature and for storage
       conditions when  the column is not in use.

4.12   BAND BROADENING AND RETENTION TIME (RT) SHIFTS IN HIGH IONIC
       STRENGTH MATRICES - Method performance has not been evaluated for matrix ion
       concentrations exceeding 320 mg/L chloride, 250 mg/L sulfate, 150  mg/L bicarbonate and 20
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          mg/L nitrate. Near these limits, the analyte peaks will widen, peak height will decrease, and
          retention times will decrease slightly. These effects are compound dependent, but affect all
          analytes to some degree.  Such effects were minimal in the drinking water matrices
          evaluated, but were more pronounced in Laboratory Synthetic Sample Matrix. [Compare
          Figure 3 (fortified tap water) and Figure 4 (fortified synthetic matrix).] Note that the
          concentrations of common anions in the LSSM are at the limits listed above.  This method
          requires the analyst to verify method performance in LSSM during the IDC, and to verify
          elution/divert windows on a daily basis in LFSSM to ensure that these windows are properly
          set to compensate for the potential effects of high ionic strength matrices.

5.    SAFETY

   5.1   The toxicity and carcinogenicity of each reagent used in this method has not been precisely
         defined.  Each chemical should be treated as a potential health hazard and exposure to these
         chemicals should be minimized.  Each laboratory is responsible for maintaining an awareness
         of OSHA regulations regarding safe handling of chemicals used in this method.3  The OSHA
         laboratory standards can be found online at
         http://www.osha.gov/SLTC/laboratories/standards.html.  A reference file of MSDSs should be
         made available to all personnel involved in the chemical  analysis.

   5.2   Pure standard materials and stock standard solutions of the method compounds should be
         handled with suitable protection for skin, eyes, etc.4

6.    EQUIPMENT AND SUPPLIES
     References to specific brands or catalog numbers are included as examples only and do not imply
     endorsement of the product. Such reference does not preclude the use of other vendors or
     suppliers.

   6.1    SAMPLE CONTAINERS - Amber glass bottles  fitted with polytetrafluoroethylene (PTFE)
          -lined screw caps with sufficient volume to allow preparation of all required sample and QC
          aliquots.

   6.2    VIALS FOR SAMPLE PREPARATION - Amber glass vials with PTFE/silicone septa for
          use preparing field samples and QC samples. Forty-milliliter (mL) volatile organic analysis
          (VOA) vials (I-Chem Cat. No. S146-0040 or equivalent) were used during method
          development.
   6.3    AUTOSAMPLER VIALS - Glass vials with PTFE/silicone septa.

   6.4    MICRO SYRINGES - Suggested sizes include 50, 100, and 1000 microliters (|iL).

   6.5    VOLUMETRIC PIPETTES - Class A, for preparing calibration standards, and for measuring
          aliquots of field samples and QC samples.
   6.6    AUTOMATIC PIPETTE -  Electronic, with polypropylene tips (Eppendorf Research Pro or
          equivalent). An automatic pipette is recommended for fortifying samples with internal
          standards.
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6.7   ANALYTICAL BALANCE - Capable of weighing to the nearest 0.0001 gram (g).

6.8   TOP-LOADING BALANCE - Capable of weighing to the nearest 0.01 g.  A top-loading
      balance and disposable pipettes may be used to measure aqueous sample volumes and to
      prepare aqueous calibration standards.

6.9   DESOLVATION GAS - High-purity gas (nitrogen or zero-air) for use in the ESI interface.
      The specific type of gas, purity and pressure requirements will depend on the instrument
      manufacturer's specifications.

6.10  COLLISION GAS - High-purity gas (nitrogen or argon) for use in the collision cell of the
      mass spectrometer.  The specific type of gas, purity, and pressure requirements will depend
      on the instrument manufacturer's specifications.

6.11  DISPOSABLE PASTEUR PIPETTES - Borosilicate glass, used to transfer samples to
      autosampler vials and for sample preparation.

6.12  ION CHROMATOGRAPHY ELECTROSPRAY IONIZATION TANDEM MASS
      SPECTROMETRY SYSTEM (IC-ESI-MS/MS) - The following specifications are based on
      use of a Dionex Corporation AS24 ion exchange column and a hydroxide-based eluent
      system. Other columns and eluent systems  are permitted providing that the basic
      chromatographic elements of the method are retained (Sect. 1.7).

    6.12.1 1C SYSTEM WITH SUPPRESSED CONDUCTIVITY DETECTION - An analytical
          system (Dionex ICS-3000 or equivalent) consisting of a refrigerated autosampler, pump
          module, anion trap, guard column, anion separator column, a six-port injection valve,
          sample loop, conductivity suppressor, conductivity detector, post-column divert valve,
          and a data acquisition and management  system. The laboratory must be able to acquire
          and store conductivity data for the purpose of monitoring matrix components and
          establishing elution/divert windows.

     6.12.1.1  ELUENT GENERATION - Reagent-free electrolytic eluent generation (Dionex ICS-
             3000 EG or equivalent) or manually prepared reagents may be used. Care must be
             exercised with manually prepared hydroxide eluent to prevent formation of carbonate
             in the eluent from exposure to the atmosphere, which could cause analyte retention
             times to drift.

     6.12.1.2  ANION TRAP - A continuously regenerated anion trap column (Dionex CR-ATC or
             equivalent).

     6.12.1.3  SAMPLE LOOP - 100-jiL size.  A 100-jiL sample loop was used to generate the data
             presented in this method. Smaller injection volumes may be used as long as the
             Initial Demonstration of Capability (Sect. 9.2), calibration, and sample analyses are
             performed using the same injection volume. The laboratory must be able to meet the
             MRL verification criteria (Section 9.2.4) using the selected injection volume.
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  6.12.1.4  GUARD COLUMN - lonPac  AG24, 2 x 50 millimeters (mm) (Dionex Part
          No. 064151 or equivalent). The guard column is generally packed with the same
          resin as the analytical column.

  6.12.1.5  ANALYTICAL COLUMN - lonPac® AS24, 2 x 250 mm (Dionex Part No. 064153
          or equivalent). Any column that provides on-line separation of common anions
          (chloride, carbonate, sulfate, and nitrate) from the method analytes and symmetrical
          peak shapes may be used. The column must have sufficient capacity to minimize
          retention time shifts in high ionic strength matrices.

  6.12.1.6  COLUMN COMPARTMENT - Temperature controlled and capable of subambient
          operation.

  6.12.1.7  CONDUCTIVITY SUPPRESSOR - An electrolytic suppressor operated with an
          external source of regeneration water (Dionex Anion Self Regenerating Suppressor
          Model No. ASRS®-300, 2-mm, Part No. 064555 or equivalent).  Chemical
          conductivity suppressors, although not prohibited, have not been evaluated for use
          with Method  557.

  6.12.1.8  CONDUCTIVITY DETECTOR - A flow-through detector with an internal volume
          that does not  introduce analyte band broadening.

  6.12.1.9  POST-COLUMN DIVERT VALVE - A two-position, six-port valve may be used.
          All wetted parts must be of polyetheretherketone (PEEK) construction. The proper
          placement of the divert valve in the sample path is illustrated in Figure 1.

6.12.2  AUXILIARY PUMP - Pump capable of precisely delivering flow rates between 0.2 and
       0.3 mL/minute. This pump is used to mix acetonitrile into the suppressed eluent post-
       column. (Dionex high performance metering pump, Model No. AXP-MS or equivalent).
       See Figure 1 for placement of the pump in the sample path.

6.12.3  STATIC MIXING TEE - High pressure,  microbore mixing tee.  (Upchurch Scientific,
       Oak Harbor, WA, Part No. U-466 or equivalent). The proper placement of the mixing tee
       in the sample path is illustrated in Figure  1.

6.12.4  ELECTROSPRAY IONIZATION - TANDEM MASS SPECTROMETER (ESI -
       MS/MS) - The mass spectrometer interface must be able to operate in the negative-ion
       electrospray ionization mode. The system must be capable of performing MS/MS to
       produce unique product ions for the method analytes within specified retention time
       windows.  Method performance data presented in Section 17 were collected using a
       Waters Quattro Premier XE ESI-MS/MS system.

6.12.5  MS/MS DATA SYSTEM - An interfaced data system is required to acquire, store, and
       output MS data.  The computer software must have the capability of processing stored
       data by recognizing a chromatographic peak within a given retention time window.  The
       software must allow integration  of the ion abundance of any specific ion between
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             specified time or scan number limits.  The software must be able to construct a linear
             regression or quadratic calibration curve and calculate analyte concentrations using the
             internal standard technique.

7.    REAGENTS AND STANDARDS

   7.1    REAGENTS AND SOLVENTS - Reagent grade or better chemicals must be used. Unless
          otherwise indicated, it is intended that all reagents will conform to the specifications of the
          Committee on Analytical Reagents of the American Chemical Society (ACS), where such
          specifications are available. Other grades may be used if all the requirements of the IDC are
          met when using these reagents.

      7.1.1   ACETONITRILE (CAS No. 75-05-8) - Post-column organic modifier.  High purity,
             demonstrated to be free of analytes and interferences (Honeywell Burdick & Jackson
             Brand®, Catalog No. 015 or equivalent).

      7.1.2   METHYL-TERTIARY-BUTYL ETHER (MtBE, CAS No. 1634-04-4) - High-
             performance liquid chromatography-grade (Sigma-Aldrich Catalog No. 34875  or
             equivalent). MtBE is used to prepare dilutions of neat standard materials.

      7.1.3   AMMONIUM CHLORIDE (NH4C1, CAS No. 12125-02-9) - Method preservative.

      7.1.4   SODIUM BICARBONATE (CAS No. 144-55-8) - Laboratory Synthetic Sample Matrix
             component.

      7.1.5   SODIUM CHLORIDE (CAS No. 7647-14-5) - Laboratory Synthetic Sample Matrix
             component.

      7.1.6   SODIUM NITRATE (CAS No.  7631-99-4) - Laboratory Synthetic Sample Matrix
             component.

      7.1.7   SODIUM SULFATE (CAS No. 7757-82-6) - Laboratory Synthetic Sample Matrix
             component.

   7.2    LABORATORY SYNTHETIC SAMPLE MATRIX (LSSM) - Prepare the LSSM at the
          concentrations listed in the table below. The required concentrations of nitrate (20 mg/L),
          bicarbonate (150 mg/L), chloride (250 mg/L), and sulfate (250 mg/L) are based on the mass
          of the anion, not the sodium salt. The NH4C1 preservative is included in the matrix. LFSSM
          QC samples (Sect. 3.13) can be prepared by diluting the Analyte PDS (Sect. 7.3.2.2) with the
          synthetic matrix solution.
                                          557-12

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Compound
Ammonium chloride
(preservative)
Nitrate anion
Bicarbonate anion
Chloride anion
Sulfate anion
Empirical
Formula
NH4C1
MV
HCCV
cr
SO4"
Salt
(gtw)a
53.49
84.99
84.01
58.44
142.04
Anion
(gtw)

62.00
61.02
35.45
96.06
Salt Mass
(mg)
500
137
1030
2060
1850
H2O, L
0.5
Cone. Stock
(mg/L)b
1000
200
1500
2500
2500
Cone. LSSM
(mg/L)c
100
20
150
250
250
     a  gfw = gram formula weight of the sodium salt.
     b  Stock concentration = (salt mass)(gfw anion)/(gfw salt)(0.5 L).
     0  1:10 dilution of stock (e.g., 50 mL to 500 mL), LSSM = Laboratory Synthetic Sample Matrix.

7.3     STANDARD SOLUTIONS - Solution concentrations listed in this section were used to
       develop this method and are included only as examples. Guidance on the storage stability of
       Primary Dilution Standards and calibration standards is provided in the applicable sections
       below.

       NOTE: When preparing aqueous solutions from MtBE stock solutions, do not add more
       than 0.5% of MtBE relative to the total water volume.  MtBE has limited water solubility
7.3.1
          INTERNAL STANDARDS - This method requires four isotopically enriched internal
          standards. The following table lists the required internal standards and current sources.
Internal Standard
Monochloroacetic acid-2-13C
Monobromoacetic acid-7-13C
Dichloroacetic acid-2-13C
Trichloroacetic acid-2-13C
CASRN"
1633-47-2
57858-24-9
286367-78-0
Not available
Neat Materials
Catalog No.
Sigma- Aldrich 488526
Sigma- Aldrich 279331
Sigma- Aldrich 485489
Custom synthesis'3
Solution Standards
(1000 ug/mL in MtBE), Cat. No.
Dionex Corp. 069406
Dionex Corp. 069407
Dionex Corp. 069408
Dionex Corp. 069409
       CASRN = Chemical Abstract Registry Number.
       Isotec, a member of the Sigma-Aldrich Group (www.sigma-aldrich.com/isotec').

     NOTE: TCAA[1-13C] may NOT be substituted for TCAA[2-13C].  TCAA[1-13C] has been
     demonstrated to convert to the native TCAA analyte in the ESI interface, theoretically via gas-
     phase exchange with carbon dioxide-12C in the ionization region of the source. The process is
     temperature dependent (desolvation gas temperature) and was observed on all MS/MS
     platforms evaluated during method development.

     7.3.1.1  INTERNAL STANDARD STOCK STANDARDS (ISSS) (1000 ug/mL) - Prepare
             individual solutions of MCAA[2-13C], MBAA[1-13C], DCAA[2-13C], and TCAA[2-
             13C] by weighing 15 mg of the solid material into a 15-mL vial and adding  15 mL of
             MtBE. Alternately, obtain the internal standards from outside suppliers as solutions
             in MtBE at 1000 ng/mL.

     7.3.1.2  INTERNAL STANDARD PRIMARY DILUTION STANDARD (Internal  Standard
             PDS) (1.0 |ig/mL) - Prepare the Internal Standard PDS by adding enough of each
             ISSS to a known volume of reagent water to make the final concentration 1.0 |ig/mL
             (e.g., combine 100 jiL of each ISSS into 100 mL reagent water).  Store the PDS in a
                                        557-13

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          glass vial with a PTFE/silicone septum.  During method development, addition of 160
          jiL of the Internal Standard PDS to each 40-mL field sample, QC sample, or
          calibration standard produced a final concentration of 4.0 |ig/L.  Analysts are
          permitted to use other PDS concentrations and volumes provided all field samples,
          QC samples, and calibration standards contain the same amount of internal standard,
          the concentration of the internal standard added provides adequate signal to maintain
          precision (as defined in the IDC), and the volume added has a negligible effect on the
          final  concentration. The aqueous Internal Standard PDS is stable for 60 days when
          stored at 4 °C.
7.3.2   ANALYTE STANDARD SOLUTIONS

  7.3.2.1   ANALYTE STOCK STANDARD SOLUTION (1000 |ig/mL) - Obtain the
          haloacetic acid analytes listed in the table in Section 1.1 as certified solutions in
          MtBE. Obtain bromate as a certified aqueous standard.  Obtain  dalapon as a certified
          standard in MtBE or in methanol. Representative sources are listed in the table in
          Section 7.3.2.2.

  7.3.2.2   ANALYTE PRIMARY DILUTION SOLUTION (Analyte PDS) (1.0 |ig/mL) -
          Prepare the Analyte PDS by diluting of the Analyte Stock Standard solutions into
          reagent water.  Store the PDS in a glass vial with a PTFE/silicone septum. The
          Analyte PDS is used to prepare calibration standards,  and to fortify QC samples with
          the method analytes. An example preparation of the Analyte PDS that was used to
          collect data presented in Section 17 is provided in the table below.
Analyte
Stock
Bromate,
aqueous
Dalapon in
methanol
Haloacetic
acids in
methyl-tert-
butyl ether
Catalogue
Number
Ultra Scientific
Cat. No. ICC-010
Ultra Scientific
Cat. No. HB-140
Restek Cat.
No. 31896
Stock
Concentration
Glg/mL)
1000 as bromate
anion
100
1000
Stock
Volume
(mL)
0.05
0.50
0.05
Final Volume
(mL reagent
water)
50
Analyte PDS
Concentration
(Hg/mL)
1.0
  7.3.2.3
NOTE: Storage stability of the Analyte PDS was evaluated during method
development at a single concentration of 1.0 ng/mL. The aqueous Analyte PDS is
stable for 60 days when stored at 4 °C. Other PDS  concentrations may be selected.
However, it is recommended that the laboratory independently assess the stability of
the aqueous PDS to determine safe storage time.

CALIBRATION STANDARDS - This method uses a procedural calibration
technique. Prepare procedural calibration  standards by diluting the Analyte PDS into
reagent water containing 100 mg/L NFLjCl (preservative).  A calibration range of 0.25
to 20 |ig/L is recommended as a starting point and is adequate for most drinking
water sources. The lowest concentration calibration standard must be at or below the
                                    557-14

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                 MRL. A constant amount of each internal standard is added to each calibration
                 standard. The calibration standards may also be used as CCCs. An example of the
                 dilutions (starting with the Analyte PDS) necessary to prepare the calibration
                 standards is provided in the table below.
Dilution Aliquot
2 mL Analyte PDS
20mLofWS
lOmLofWS
SmLofWS
2mLofWS
ImLofWS
4 mL of 5 jig/L std.
2 mL of 5 |ig/L std.
Starting
Concentration
(Ug/L)
1000
40
40
40
40
40
5.0
5.0
Final Volume (mL,
100 mg/L ammonium
chloride, aqueous)
50
40
40
40
40
40
40
40
Final
Concentration
(Ug/L)
40 (WS)a
20
10
5.0
2.0
1.0
0.50
0.25
Internal Standard
Concentration"
(Ug/L)
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
           Internal standards added at the rate of 160 |jL to 40 mL by use of an Eppendorf Research Pro pipette:
                      (0.16 mL)(1.0 |j,g/mL)/(0.040 liter) = 4.0 |j.g/L internal standard concentration
           WS = working standard; not analyzed.

                NOTE: The stability of calibration standards was evaluated during method
                development at concentrations of 2.0 and 5.0 |ig/L.  The aqueous calibration
                standards are stable for 14 days when stored at 4 °C in glass vials with PTFE/silicone
                septa. It is recommended that the laboratory independently assess the stability of the
                aqueous calibration standards to determine safe storage time.

8.    SAMPLE COLLECTION, PRESERVATION, AND STORAGE

     The preservation requirements for Method 557 are identical to those stipulated in EPA Method
     552.3, Determination ofHaloacetic Acids andDalapon in Drinking Water by Liquid-Liquid
     Microextraction, Derivatization, and Gas Chromatography with Electron Capture Detection^

   8.1   SAMPLE BOTTLE PREPARATION

       8.1.1  SAMPLE CONTAINERS - Amber glass bottles with PTFE-lined screw caps and
             sufficient capacity to allow subsequent preparation of all required sample and QC
             aliquots.

       8.1.2  ADDITION OF PRESERVATIVE - Prior to shipment to the field, add crystalline or
             granular NFLjCl to the sample containers to produce a concentration of 100 mg/L in the
             field sample. For example,  a 250-mL sample requires 25 mg of NFLiCl.

   8.2   SAMPLE COLLECTION - Grab samples must be collected in accordance with conventional
         sampling practices.6 Fill sample bottles taking care not to flush out the ammonium chloride.
         Because the method analytes are not volatile, it is not necessary to ensure that the sample
         bottles are completely headspace-free.
                                            557-15

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       8.2.1  SAMPLING FROM A TAP - When sampling from a cold water tap, remove the aerator,
             open the tap, and allow the system to flush until the water temperature has stabilized
             (approximately three to five minutes).  Collect a representative sample from the flowing
             system using a beaker of appropriate size. Use this bulk sample to generate individual
             samples as needed. Invert the vials several times to mix the sample with the preservation
             reagent.

   8.3   SAMPLE SHIPMENT AND STORAGE - Samples must be chilled during shipment and
         must not exceed 10 °C during the first 48 hours after collection.  Samples must be confirmed
         to be at or below 10 °C when they are received at the laboratory. In the laboratory, samples
         must be stored at or below 6 °C and protected from light until analysis. Samples must not be
         frozen.

   8.4   SAMPLE HOLDING TIMES - Samples must be analyzed within 14 days of collection.
         Chlorinated field samples that are preserved in accordance with the method guidance should
         not exhibit biological degradation of analytes during the allotted 14-day storage time.  The
         residency time in the autosampler must be included when calculating the holding time
         from collection until analysis.

9.    QUALITY CONTROL

   9.1   QC requirements include the IDC and ongoing QC requirements. This section describes each
         QC parameter, its required frequency, and the performance criteria that must be met in order
         to satisfy EPA quality objectives. The QC criteria discussed in the following sections are
         summarized in Section 17, Tables 11  and 12. These QC requirements are considered the
         minimum acceptable QC program. Laboratories are encouraged to institute additional QC
         practices to meet their specific needs.

   9.2   INITIAL DEMONSTRATION OF CAPABILITY (IDC) - The IDC must be successfully
         performed prior to analyzing any field samples. The IDC must be repeated if changes are
         made to analytical parameters not previously validated during the IDC, for example, selection
         of an alternate MRM transition or changing the internal standard assignment of an analyte.
         Prior to conducting the IDC, the analyst must verify proper timing of elution windows and
         divert windows (Section 10.2.5), and  meet the  calibration requirements outlined in Sections
         10.2 and 10.3.

       9.2.1  DEMONSTRATION OF LOW SYSTEM BACKGROUND - Analyze an LRB.
             Confirm that the blank is free of contamination as defined in Section 9.3.1.

             NOTE: Depending on the source and purity, labeled haloacetic acid internal standards
             may contain a small percentage of the corresponding native analyte.  Therefore, the
             analyst must demonstrate that the internal standards do not contain the unlabeled analytes
             at a concentration >l/3 of the MRL when  added at the appropriate concentration to
             samples. An internal standard concentration of 4.0 |ig/L was used during method
             development. Lower concentrations may be used providing the internal standard QC
             criteria (Sect.  9.3.4) are met.
                                           557-16

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       NOTE: The method must be checked for cross contamination (commonly referred to in
       the environmental laboratory community as "carryover") by analyzing an LRB
       immediately following the highest calibration standard.  If this LRB does not meet the
       criteria outlined in Section 9.3.1, then carryover is present and the cause must be
       identified and eliminated.

9.2.2   DEMONSTRATION OF PRECISION - Prepare and analyze seven replicate LFBs and
       seven replicate LFSSMs. Fortify these samples near the midrange of the initial
       calibration curve. The NH4C1 preservative must be added to the LFBs as described in
       Section 8.1.2. The percent relative standard deviation (RSD) of the concentrations of the
       replicate analyses must be <20% for all method analytes.

                   _ Standard Deviation of Measured Concentrations
             /o RSD — - X 1 00
                                Average Concentration

9.2.3   DEMONSTRATION OF ACCURACY  - Using the same sets of replicate data generated
       for Section 9.2.2, calculate the average percent recovery. The average percent recovery
       of the replicate analyses  must be within +30% of the true value.

                .. _.          Average Measured Concentration  , ^
                % Recovery = - - - x 1 00
                                  Fortified Concentration

9.2.4   MINIMUM REPORTING LEVEL (MRL) CONFIRMATION - Establish a target
       concentration for the MRL based on the  intended use of the method.  Analyze an initial
       calibration following the procedures in Section 10.3. The lowest calibration standard
       used to establish the initial calibration (as well as the low-level CCC) must be at or below
       the concentration of the MRL. Establishing the MRL concentration too low may cause
       repeated failure of ongoing QC requirements. Confirm the MRL following the procedure
       outlined below.

  9.2.4. 1   Fortify and analyze seven replicate LFBs at or below the proposed MRL
          concentration. The LFBs must contain the method preservative as specified in
          Section 8. 1 .2. Calculate the mean (Mean) and standard deviation for these replicates.
          Determine the Half Range for the Prediction Interval of Results (HRPIR) using the
          equation

                                 HRPIR = 3.9638

          where S is the standard deviation and 3.963 is a constant value for seven replicates.1

  9.2.4.2   Confirm that the Upper and Lower limits for the Prediction Interval of Results (PIR =
          Mean +_ HRpiR) meet the upper and lower recovery limits as shown below.
          The Upper PIR Limit must be <150 percent recovery.
                                     557-17

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                               Mean + HR
                                          P1R
                                                 xlOO< 150%
                           FortifiedConcentration

          The Lower PIR Limit must be >50 percent recovery
                               Mean - HR
                                          PIR
                           FortifiedConcentration
                                                 xlOO> 50%
  9.2.4.3   The MRL is validated if both the Upper and Lower PIR Limits meet the criteria
          described above. If these criteria are not met, the MRL has been set too low and must
          be confirmed again at a higher concentration.

          NOTE: These equations are only valid for seven replicate samples.

9.2.5   QUALITY CONTROL SAMPLE (QCS) - Analyze a mid-level Quality Control Sample
       (Sect. 9.3.7) to  confirm the accuracy of the primary calibration standards.

9.2.6   DETECTION LIMIT DETERMINATION (optional) - While DL determination is not a
       specific requirement of this method, it may be required by various regulatory bodies
       associated with compliance monitoring. It is the responsibility of the laboratory to
       ascertain whether DL determination is required based upon the intended use of the data.

       Analyses for this procedure must be done over at least three days. Prepare at least seven
       replicate LFBs  at a concentration estimated to be near the DL. This concentration may be
       estimated by selecting a concentration at two to  five times the noise level.  The NtLjCl
       preservative must be added to the samples as described in Section 8.1.2. Process the
       seven replicates through all steps of Section  11.

       NOTE:  If an MRL confirmation data set meets these requirements, a DL may be
       calculated from the MRL confirmation data, and no additional analyses are necessary.

             Calculate the DL using the following equation:

                              DL = S X t(n_i5i_a = o.99)

             where
             t(n-i,i-a = 0.99) = Student's t value for the 99%  confidence level with n-1 degrees of
                            freedom  (for seven replicate determinations, the Student's t value
                            is 3.143 at a 99% confidence level),
             n = number of replicates, and
             S = standard deviation of replicate analyses.

       NOTE:  Do not subtract blank values when performing DL  calculations.
                                     557-18

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9.3     ONGOING QC REQUIREMENTS - This section describes the ongoing QC elements that
       must be included when processing and analyzing field samples. Table 12 summarizes these
       requirements.

   9.3.1   LABORATORY REAGENT BLANK (LRB) - Analyze an LRB during the IDC and
          with each Analysis Batch. The LRB must contain the NH/iCl preservative and the
          internal standards at the same concentration used to fortify all field samples and
          calibration standards.  Background from method analytes or contaminants that interfere
          with the measurement of method analytes must be 
-------
          repeat analysis, but passes in the most recent CCC, report the sample results as
          "suspect/matrix."

9.3.5   LABORATORY FORTIFIED SAMPLE MATRIX (LFSM) - Within each Analysis
       Batch, analyze a minimum of one LFSM.  The background concentrations of the analytes
       in the sample matrix must be determined in a separate aliquot and subtracted from the
       measured values in the LFSM. If various sample matrices are analyzed regularly, for
       example, drinking water processed from ground water and surface water sources,
       performance data must be collected for each source.

  9.3.5.1   Prepare the LFSM by fortifying a sample with an appropriate amount of the Analyte
          PDS (Sect. 7.3.2.2). Generally, select a spiking concentration that is greater than or
          equal to the native concentration for most analytes.  If the native concentrations of
          method analytes do not allow this criterion to be met without exceeding the
          calibration range, dilution with reagent water containing NFLjCl (100 mg/L) is
          permitted. Selecting a duplicate aliquot of a sample that has already been analyzed
          aids in  the selection of an appropriate spiking level.  If this is not possible, use
          historical data when selecting a fortifying concentration.

  9.3.5.2   Calculate the percent recovery (%R) using the equation:
                                        C
          where
          A = measured concentration in the fortified sample,
          B = measured concentration in the unfortified sample, and
          C = fortification concentration.

  9.3.5.3   Recoveries for samples fortified at concentrations near or at the MRL (within a factor
          of two times the MRL concentration) must be within +50% of the true value.
          Recoveries for samples fortified at all other concentrations must be within +30% of
          the true value.  If the accuracy for any analyte falls outside the designated range, and
          the laboratory performance for that analyte is shown to be in control in the CCCs, the
          recovery is judged matrix biased.  Report the result for the corresponding analyte in
          the unfortified  sample as "suspect/matrix."

          NOTE:  In order to obtain meaningful percent recovery results, correct the measured
          values in the LFSM and LFSMD for the native levels in the unfortified samples,  even
          if the native values are less than the MRL.  This situation and the LRB are the only
          permitted uses  of analyte results below the MRL.

9.3.6   LABORATORY DUPLICATE OR LABORATORY FORTIFIED SAMPLE MATRIX
       DUPLICATE (LD or LFSMD) - Within each Analysis Batch, analyze a minimum of one
       Laboratory Duplicate or one Laboratory Fortified Sample Matrix Duplicate.  If the
       method analytes are not routinely observed in field samples, analyze an LFSMD rather
       than an LD.
                                     557-20

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          NOTE: The variation due to the addition of internal standards must be included in the
          precision estimate.  Therefore, first split the original sample and then fortify each aliquot
          with internal standards.

     9.3.6.1  Calculate the relative percent difference (RPD) for duplicate measurements (LDi and
             LD2) using the equation:

                                       ILD, -LD,
                              RPD =
                                     (LDj+LDj/2'

     9.3.6.2  RPDs for Laboratory Duplicates must be <30%.  Greater variability may be observed
             when Laboratory Duplicates have analyte concentrations that are near or at the MRL
             (within a factor of two times the MRL concentration).  At these concentrations,
             Laboratory Duplicates must have RPDs that are <50%.  If the RPD of an analyte falls
             outside the designated range, and the laboratory performance for the analyte is shown
             to be in control in the CCC, the precision is judged matrix influenced. Report the
             result for the corresponding analyte in the unfortified sample as "suspect/matrix."

     9.3.6.3  If an LFSMD is analyzed instead of a Laboratory Duplicate, calculate the RPD for the
             LFSM and LFSMD using the equation:

                                   ILFSM-LFSMD
                           RPD=-!	—xlOO
                                  (LFSM+LFSMD )/2


     9.3.6.4  RPDs for duplicate LFSMs must be <30%. Greater variability may be observed when
             the matrix is fortified at analyte concentrations near or at the MRL (within a factor of
             two times the MRL concentration). LFSMs at these concentrations must have RPDs
             that are <50%. If the RPD of an analyte falls outside the designated range, and the
             laboratory performance for the analyte is shown to be in control in the CCC, the
             precision is judged matrix influenced.  Report the result for the corresponding analyte
             in the unfortified sample as "suspect/matrix."

   9.3.7  QUALITY CONTROL SAMPLE (QCS) - A QCS must be analyzed during the IDC, and
          then at least quarterly thereafter.  Fortify the QCS near the midpoint of the calibration
          range. The acceptance criteria for the QCS are the same as the mid- and high-level CCCs
          (Sect. 10.4).  If the accuracy for any analyte fails the recovery criterion, prepare fresh
          standard dilutions and repeat the QCS evaluation.

9.4    METHOD MODIFICATION QC REQUIREMENTS - The laboratory is required to perform
       the procedures in this section if chromatographic conditions and a suppression technique are
       selected which are different from those utilized to develop the method.  Any proposed
       method modifications must retain the basic chromatographic elements of this new technique
       (Sect. 1.7). Examples of method modifications include alternate 1C columns, an injection
       volume less than 100 uL, and additional internal standards proposed for use with the method.


                                        557-21

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       9.4.1  Each time method modifications are made, optimize the elution gradient to accomplish
             separation of the method analytes from matrix components, and then verify elution and
             divert windows following the guidance in Section 10.2.5. Establish an acceptable initial
             calibration (Sect.  10.3).  Finally, repeat the procedures of the IDC (Sect. 9.2).

       9.4.2  The analyst is also required to evaluate and document method performance for the
             proposed modifications in real matrices that span the range of waters that the laboratory
             analyzes. This additional step is required because modifications that perform acceptably
             in the IDC, which is conducted in reagent water and synthetic matrix, could fail ongoing
             method QC requirements in real matrices. This is particularly important for methods
             subject to matrix effects, such as IC/MS-based methods. For example, a laboratory may
             routinely analyze drinking water from municipal treatment plants that process ground
             water,  surface water, or a blend of surface and ground water. In this case, the method
             modification requirement could be accomplished by assessing precision and accuracy
             (Sects. 9.2.2 and 9.2.3) in a surface water with moderate to high total organic carbon
             (e.g., 2 mg/L or greater) and a hard ground water (e.g., 250 mg/L as calcium carbonate
             (CaCOs) equivalent, or greater).

       9.4.3  The results of Sections 9.4.1 and 9.4.2 must be appropriately documented by the analyst
             and independently assessed by the laboratory's QA officer prior to analyzing field
             samples. When implementing method modifications, it is the responsibility of the
             laboratory to closely review the results of ongoing QC, and in particular, the results
             associated with the LFSM (Sect. 9.3.5), LFSMD (Sect. 9.3.6), CCCs (Sect. 9.3.2), and
             the internal standard area counts (Sect. 9.3.4).  If repeated failures are noted, the
             modification must be abandoned.

10   CALIBRATION AND STANDARDIZATION

   10.1   Demonstration and documentation of acceptable MS calibration and initial analyte
          calibration are required before performing the IDC and prior to analyzing field samples.
          Prior to calibration, the analyst must verify the proper timing of divert windows as described
          in Section 10.2.5.  The initial calibration must be repeated each time a major instrument
          modification or maintenance is performed.

   10.2   IC-ESI-MS/MS CALIBRATION AND OPTIMIZATION

       10.2.1 MASS CALIBRATION - Method 557 requires the monitoring of low-mass, negatively
             charged ions within nominal m/z range of 35 to 251.  Calibrate the mass spectrometer
             with the calibration compounds and procedures specified by the manufacturer. Verify the
             mass assignment accuracy for each precursor ion and each product ion by comparing the
             reported centroid mass to the theoretical mass. (Pay particular attention to the chlorine
             product ion at nominal m/z 35, actual m/z 34.97.) Low signal response could result if
             mass assignments are not centered on the detected mass peaks. If the reported masses
             differ from the calculated masses and low response is observed, the standard calibration
             procedure may be inadequate for this method.  Consult the MS/MS manufacturer for an
                                            557-22

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       appropriate low-mass calibration procedure. During method development, accurate mass
       assignments were achieved after calibration via direct infusion of sodium formate
       (10 nanograms per microliter) in 90:10 2-propanol:water, rather than the sodium iodide
       and cesium iodide mixture typically employed for Waters MS/MS systems.

10.2.2  OPTIMIZING MS PARAMETERS - Each IC-ESI-MS/MS system will have different
       optimal conditions, which are influenced by the source geometry and system design. Due
       to the differences in design, follow the recommendations of the instrument manufacturer
       when tuning the instrument.  During the development of this method, instrumental
       parameters were optimized for the precursor and product ions listed in Section 17, Table
       3. Because the method analytes are relatively small molecules, the selection of precursor
       and product ions is limited. However, transitions other than those listed exist, and the
       optimum choice depends on the instrument platform as noted below.

       NOTE: Several instrument platforms were investigated during method development.
       The most abundant precursor ions differed depending on the design of the ESI interface.
       In particular, the trihaloacetic acids containing bromine tend to undergo neutral loss in
       the ESI interface. For example, the precursor ions for BDCAA, CDBAA, and TBAA
       used during method development (Table 3) are 44 mass units less than the molecular ion,
       corresponding to loss of a carboxyl group (COO"). However, using other ESI designs,
       the m/z 207 precursor ion for BDCAA was  observed, which corresponds to the mass of
       the molecular ion. BDCAA and TBAA exhibited neutral loss on all ESI-MS/MS systems
       evaluated.  The most abundant product ions also differed between instruments. Although
       the mass transitions in Table 3 are provided as a guide, the analyst must empirically
       determine the most abundant precursor and product ions.

  10.2.2.1  Optimize the ESI-MS/MS at the analytical flow rate (column eluent plus post-column
          acetonitrile addition) via split infusion or flow injection analysis (FIA).  Use solutions
          having concentrations between 1 and 5  |ig/mL of the method analytes in reagent
          water for split infusion, and solutions having concentrations between 10 and 100 |ig/L
          (0.01 and 0.1 |ig/mL) in reagent water for FIA. Five- or 10-|iL sampling loops are
          recommended for optimizing via FIA.  Because the precursor and product ions may
          be identical for some of the haloacetic acids, individual solutions of the method
          analytes are recommended for this step.

  10.2.2.2 Using Table 3 as a guide, select the most abundant precursor ion. Optimize the
          response of the precursor ion for each analyte by infusing the prepared  solutions
          (Sect. 10.2.2.1) directly into mobile phase (or via FIA). Vary the ESI parameters
          (probe orientation, capillary extension, source voltages, source and  desolvation
          temperatures, gas flows, etc.) and the MS parameters until optimal analyte responses
          are determined.  The method analytes may have different optima, thus requiring some
          compromise.  ESI-MS/MS systems are subject to drift, which can affect run-to-run
          precision.  Accordingly, the optimal conditions may be those that yield adequate
          response while minimizing the potential for drift.
                                     557-23

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  10.2.2.3  Using Table 3 as a guide, select the most abundant product ion. Optimize the
          response of the product ion for each analyte by infusing the prepared solutions (Sect.
          10.2.2.1) directly into the mass spectrometer (or via FIA). Vary the MS/MS
          parameters (collision gas pressure, collision energy, etc.) until optimal analyte
          responses are determined.

10.2.3 ION CHROMATOGRAPHY INSTRUMENT CONDITIONS - Follow the column
      manufacturer's guidelines for calculating the elution gradient to accomplish separation of
      the method analytes from matrix components.  1C operating conditions for the Dionex
      AS24 column7 used during method development are summarized in Section 17, Table 1.
      Establish divert windows for the matrix components and elution windows for the method
      analytes per the column manufacturer's instructions. Figure  2 presents an example of
      these windows optimized for the Dionex AS24 column.  Conditions different from those
      described in this method (e.g., 1C columns and mobile phases) may be used if the QC
      criteria in Sections 9.2, 9.3 and 9.4 are met, the column provides reasonable resolution of
      the method analytes, and chromatographic separation of the method analytes from matrix
      anions (chloride, carbonate, sulfate, nitrate) is achieved.

10.2.4 ESTABLISH IC-ESI-MS/MS RETENTION TIMES AND MRM SEGMENTS - Inject a
      mid- to high-level calibration standard under optimized IC-ESI-MS/MS conditions to
      obtain the retention times of each method analyte.  Divide the chromatogram into
      segments that contain one or more chromatographic peaks. For maximum sensitivity in
      subsequent MS/MS analyses, minimize the number of MRM (Sect. 3.19) transitions that
      are simultaneously monitored within each segment. Table 2  presents the assignment of
      the method analytes and internal standards into each of the three MRM windows used
      during method development.

10.2.5 VERIFY ELUTION AND DIVERT WINDOWS FOR MATRIX ELIMINATION -
      Conduct the following tests and verify that the timing of the elution and divert windows
      meet the stated criteria.

   10.2.5.1 Stabilize the chromatographic system and analyze an LFSSM at 10 |ig/L. Locate
           the first and last analyte peak in each elution window. Display the corresponding
           conductivity trace and note the peak start and peak end times for the chloride,
           carbonate, sulfate, and nitrate matrix anions.  Consider a conductivity signal of
           ~5 jiS as the peak end (return to baseline) after elution of a matrix anion.  [Refer to
           figures 4 and 5 for an example based on use of the Dionex AS24 column. For this
           column, the chloride anion elutes between elution window 1 and elution window 2.
           Carbonate, sulfate and nitrate anions elute between elution windows 2 and 3.]

   10.2.5.2 For the first analyte in each elution window, calculate a maximum time for the
           preceding valve switch: RT - (1.5)(peak width at base of the first analyte in the
           window). For the last analyte in each elution window, calculate a minimum time for
           the following valve switch:  RT + (1.5)(peak width at base of the last analyte in the
           window). Verify that the valve switch times set in step 10.2.3 do not overlap the
           calculated times.
                                    557-24

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               NOTE: The actual valve switch times are set in accordance with the column
               manufacturer's guidelines (Section 10.2.3).  These could be wider than the start and
               end times for the elution windows calculated using the equations in this section.

       10.2.5.3 By inspection, verify that matrix peaks have returned to baseline before the
               calculated valve switch at the beginning of each elution window. By inspection,
               verify that the valve switch at the beginning of each divert window occurs before a
               matrix component begins to elute. Finally, verify that each analyte elutes entirely
               within the established elution windows. If these conditions are not met, consult the
               column manufacturer's guidelines for adjusting the elution gradient and reset the
               timing of the divert valve accordingly.

               NOTE: Enough time should be allowed for the baseline to stabilize between the
               valve  switch that begins each elution window and the appearance of the subsequent
               analyte signal.  If the valve switch is too close to the analyte, the starting point of
               the analyte peak may be difficult to distinguish from the baseline disruption,
               especially for low analyte concentrations.

10.3    INITIAL CALIBRATION

   10.3.1  CALIBRATION STANDARDS - Prepare a set of at least five calibration standards as
          described in Section 7.3.2.3.  The analyte concentrations in the lowest calibration
          standard must be at or below the MRL. Field samples must be quantified using a
          calibration  curve that spans the same concentration range used to collect the IDC data
          (Sect. 9.2),  i.e., analysts are  not permitted to use a restricted calibration range to meet the
          IDC criteria and then use a larger dynamic range during analysis of field samples.

   10.3.2  CALIBRATION - Calibrate the IC-ESI-MS/MS system using peak areas and the internal
          standard technique.  Fit the calibration points with either a linear regression or quadratic
          regression (response vs. concentration).  Weighting may be used.  Forcing the calibration
          curve through the origin is not recommended. The MS/MS instrument used during
          method development was calibrated using inverse concentration-weighted quadratic
          curves.

          NOTE: Internal standard assignments appropriate for the Dionex AS24 column for each
          method analyte are presented in Table 3, and the mass transitions for the internal
          standards are provided in Table 4.  MCAA must always be referenced to MCAA[2-13C].
          MBAA must always be referenced to MBAA[1-13C]. Method 557 was validated with
          bromate referenced to MBAA[1-13C]; however, MCAA[2-13C] could be used if all
          requirements in the IDC are met, as well as all ongoing QC requirements.

   10.3.3  CALIBRATION ACCEPTANCE CRITERIA - Validate the initial calibration by
          calculating the concentration of the analytes for each of the analyses used to generate the
          calibration  curve by use of the regression equations. Calibration points that are 
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             calculate to be within +30% of their true value. If these criteria cannot be met, the
             analyst will have difficulty meeting ongoing QC criteria.  In this case, corrective action is
             recommended such as reanalyzing the calibration standards, restricting the range of
             calibration, or performing instrument maintenance.

   10.4   CONTINUING CALIBRATION CHECKS (CCCs) - Analyze a CCC to verify the initial
          calibration at the beginning of each Analysis Batch, after every tenth field sample, and at the
          end of each Analysis Batch.  The beginning CCC for each Analysis Batch must be at or
          below the MRL.  This CCC verifies instrument sensitivity prior to the analysis of samples.
          Alternate subsequent CCCs between the remaining calibration levels.

       10.4.1 Verify that the absolute areas of the quantitation ions of each of the internal standards
             have not changed by more than ±50% from the average areas measured during the initial
             calibration. If this limit is exceeded, verify that the background conductivity is in control
             following the guidance in Section  11.3.2.  If the background conductivity is normal,
             remedial action may necessary (Sect. 10.4.3).

       10.4.2 Calculate the concentration of each analyte in the CCC. The CCC fortified at 
-------
          standards at or below 6 °C at all times, including the time these are resident in the
          autosampler awaiting injection.

   11.2.2 Do not filter the samples. Add an appropriate volume of the Internal Standard PDS (Sect.
          7.3.1.2) to a known volume of sample, cap, and mix well.  The concentration of the
          internal standards must be the same in the samples as in the calibration standards.
          Transfer an aliquot of each field or QC sample to an autosampler vial.  For example,
          weigh 40 mL of sample into a 40-mL VOA vial using a top loading balance and a
          disposable, glass pipette. Add 160 uL of the internal standard PDS (1.0 jig/mL) to
          achieve a concentration of 4.0  |ig/L in the sample.  Mix well and transfer 1.5 mL to an
          autosampler vial by use a disposable pipette.

11.3    SAMPLE ANALYSIS

   11.3.1 Establish IC-ESI-MS/MS operating conditions per the guidance in Section 10.2.

   11.3.2 Flush the column at the highest eluent concentration in the gradient for at least 15
          minutes prior to beginning each analysis sequence. This step is especially important for
          minimizing background conductivity if the column has been installed in the system and
          held at the starting eluent concentration for extended periods.

          NOTE: During method development, the background conductivity ranged from 0.3 to
          2.2 microsiemens (|iS).  If an internal standard or analyte area response is low due to high
          background conductivity, flush the column at the maximum eluent concentration in the
          gradient and observe the conductivity signal until the background stabilizes at less than
          2.5 jiS. Also, ensure that the suppressor is functioning properly or replace the suppressor
          to troubleshoot the problem. Occasional overnight flushing of the column will minimize
          the occurrence of high background conductivity.

   11.3.3 VERIFY ELUTION AND DIVERT WINDOWS - Analyze Laboratory Synthetic Sample
          Matrix fortified at 10 |ig/L. Verify the elution and divert windows as specified in Section
          10.2.5. This verification must be done prior to beginning each Analysis Batch.

   11.3.4 THE ANALYSIS BATCH - Establish a valid initial calibration following the procedures
          outlined in Section 10.3 and confirm that the calibration is valid by analyzing a CCC at or
          below the MRL as described in Section 10.4. Alternately, verify that an existing
          calibration, established for a previous Analysis Batch, is still valid by analyzing a CCC at
          or below the MRL. Next, analyze an LRB. Continue the Analysis Batch by analyzing
          aliquots of field and QC samples at appropriate frequencies (Section 9.3), employing the
          optimized conditions used to acquire the initial calibration.  Analyze a mid- or high-level
          CCC after every ten field samples and at the end each Analysis Batch.

          NOTE: Each Analysis Batch must begin with the analysis of a CCC at or below the
          MRL for each analyte that the laboratory intends to report, followed by the analysis of an
          LRB.  This is true whether or not an initial calibration is analyzed. After 20 field samples
          the low-level CCC and the LRB must be repeated to begin a new Analysis Batch. The
                                        557-27

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             acquisition start time of the mid-level CCC at the end of the Analysis Batch must be
             within 30 hours of the acquisition start time of the low-level CCC at the beginning of the
             Analysis Batch. Do not count QC samples (LRBs, LDs, LFSMs, LFSMDs) when
             calculating the frequency of CCCs that are required during an Analysis Batch.

12.  DATA ANALYSIS AND CALCULATIONS

   12.1   Establish an appropriate retention time window for each analyte to identify them in QC and
          field sample chromatograms. Base this assignment on measurements of actual retention time
          variation for each compound in standard solutions over the course of time. The suggested
          variation is plus or minus three times the standard deviation of the retention time for each
          compound for a series of injections. The injections from the initial calibration and from the
          IDC  (Sect. 9.2) may be used to calculate the retention time window.  However, the
          experience of the analyst should weigh heavily on the determination of an appropriate range.

   12.2   At the conclusion of data acquisition, use the same  software settings established during the
          calibration procedure to identify peaks of interest in the predetermined retention time
          windows. Confirm the identify of each analyte by comparison of its retention time  with that
          of the corresponding analyte peak in an initial calibration standard or CCC.

   12.3   Calculate analyte concentrations using the multipoint calibration established in Section 10.3.
          Report only those values that fall  between the MRL and the highest calibration standard.
          Samples with analyte responses that exceed the highest calibration standard require dilution
          and reanalysis (Sect. 12.7).

          NOTE: In validating this method, concentrations were calculated using the product ions
          listed in Table 3 of Section 17.  Other ions may be  selected at the discretion of the analyst as
          discussed in Section 10.2.2.

   12.4   Calculations must use all available digits of precision, but final reported concentrations
          should be rounded to an appropriate number of significant figures (one digit of uncertainty),
          typically two, and not more than three significant figures.

   12.5   Prior to reporting the data, the chromatograms must be reviewed for any incorrect peak
          identifications or improper integration.

   12.6   Prior to reporting data, the laboratory is responsible for ensuring that QC requirements have
          been met and that any appropriate qualifier is assigned.

   12.7   EXCEEDING THE CALIBRATION RANGE - The analyst must not extrapolate beyond the
          established calibration range. If an analyte result exceeds the range of the initial calibration
          curve, the sample may be diluted  using reagent water containing 100 mg/L NH4C1 with the
          appropriate amount of internal standard added to match the original level. Re-inject the
          diluted sample.  Incorporate the dilution factor into final concentration calculations. The
          resulting data must be annotated as a dilution, and the reported MRLs must reflect the
          dilution factor.
                                            557-28

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13.   METHOD PERFORMANCE

   13.1   PRECISION, ACCURACY, AND DETECTION LIMITS - The method performance data
          presented in Section 17 were collected using the 1C conditions listed in Table 1 and the
          Waters Quattro Premier XE ESI-MS/MS system. ESI-MS/MS conditions for the Waters
          system are presented in Table 2.  Tables 3 and 4 list the mass transitions for each analyte and
          internal standard, internal standard assignments, and observed retention times associated with
          the method performance results.  LCMRLs and DLs are presented in Tables 5 and 6.  Single
          laboratory precision and accuracy data are presented for four water matrices:  reagent water
          (Table 7), LSSM (Table 8), chlorinated (finished) ground water (Table 9), and chlorinated
          (finished) surface water (Table 10).  Figure 1 depicts the post-column  sample path as
          previously cited in this document (Sect. 6.12). Figures 2 through 4 are chromatograms of the
          method analytes in reagent water, drinking water, and LSSM obtained under the conditions
          employed during method development. Figure 4 was acquired with the inclusion of mass
          transitions for the chlorite and chlorate anions to mark their position in the chromatogram
          relative to the method analytes.  Figure 5 is a corresponding conductivity trace for the analyte
          chromatogram presented in Figure 4 showing the location of matrix anions, chlorite anion,
          and chlorate anion.

   13.2   SECOND LABORATORY EVALUATION - The performance of this method was
          demonstrated by a second laboratory using an API 4000 triple quadrupole mass spectrometer
          (Applied Biosystems, Foster City, CA) with results similar to those reported in Section 17.
          The authors wish to acknowledge the Southern Nevada Water Authority (Las Vegas, NV) for
          their contribution to the method development effort.

14.   POLLUTION PREVENTION

   14.1   For information about pollution prevention that may be applicable to laboratory operations,
          consult "Less is Better: Laboratory Chemical Management for Waste Reduction" available
          from the American Chemical Society's Department of Government Relations and Science
          Policy, 1155 16th Street N.W., Washington, D.C., 20036, or online at
          http://www.ups.edu/x7432.xml.

15.   WASTE MANAGEMENT

   15.1   The analytical procedures described in this method generate relatively small amounts of
          waste since only small amounts of reagents and solvents are used. The matrix of concern is
          finished drinking water. However, the Agency requires that laboratory waste management
          practices be conducted consistent with all applicable rules and regulations, and that
          laboratories protect the air, water, and land by minimizing and controlling all releases from
          fume hoods and bench operations. In addition, compliance is required with any sewage
          discharge permits and regulations, particularly the hazardous waste identification rules and
          land disposal restrictions. For further information on waste management, see the
          publications of the American Chemical Society's Laboratory Environment, Health &  Safety
          Task Force on the Internet at http://membership.acs.Org/c/ccs/publications.htm. Additional
                                            557-29

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          waste management information can be found in "Laboratory Waste Minimization and
          Pollution Prevention," Copyright © 1996 Battelle Seattle Research Center, which can be
          located at http://www.p2pavs.org/ref/01/text/00779/ch05.htm.

16.  REFERENCES

1.  Winslow, S. D.; Pepich, B. V.; Martin, J. I; Hallberg, G. R.; Munch D. I; Frebis, C. P.; Hedrick, E.
   J.; Krop, R. A. Statistical Procedures for Determination  and Verification of Minimum Reporting
   Levels for Drinking Water Methods. Environ. Sci. Technol. 2006; 40, 281-288.

2.  Glaser, J.A.; Foerst, D.L.; McKee, G.D.; Quave, S.A.; Budde, W.L. Trace Analyses for
   Wastewaters. Environ. Sci. Technol. 1981; 15, 1426-1435.

3.  Occupational Exposures to Hazardous Chemicals in Laboratories; 29 CFR 1910.1450, Occupational
   Safety and Health Administration, 1990.

4.  Safety in Academic Chemistry Laboratories; American Chemical Society Publication, Committee on
   Chemical Safety, 7th Edition: Washington, D.C., 2003.

5.  Determination ofHaloacetic Acids andDalapon in Drinking Water by Liquid-Liquid
   Microextraction, Derivatization, and Gas Chromatography with Electron Capture Detection; U.S.
   EPA Method 552.3, EPA 815-B-03-002.

6.  Standard Practice for Sampling Water from Closed Conduits; ASTM Annual Book of Standards,
   Section 11, Volume 11.01, D3370-08; American Society for Testing and Materials: Philadelphia,
   PA, 2008.

7.  Application Note 277, Dionex Corp., Sunnyvale, CA.
                                           557-30

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17.  TABLES, DIAGRAMS, FLOWCHARTS, AND VALIDATION DATA

TABLE 1.    ION CHROMATOGRAPHIC CONDITIONS USED TO COLLECT METHOD
             PERFORMANCE DATA
Parameter
Column
Precolumn
Column compartment
temperature
Hydroxide gradient
Eluent flow rate
Post-column solvent
Suppressor
Matrix diversion divert
windows
Sample volume
Conditions"
Dionex lonPac® AS24 250 mm x 2 mm i.d.
Dionex lonPac® AG24 50 mm x 2 mm i.d.
oc Autosampler tray „„
temperature
7 mM for -1 to!6.8 min, then 18 mM for 16.8 to 34.2 min, then 60 mM
for 34.4 to 5 1 .2 min, then 7 mM for 5 1 .4 to 56 min
0.30 mL/min
100% acetonitrile at 0.2 mL/min
Dionex ASRS 300 2 mm, external water mode
0 to 8 min, 16.5 to 21.2 min, and 33 to 39.2 min
100-jiLloop
   The chromatograms presented in Figures 2, 3, 4, and 5 were obtained under these conditions.
TABLE 2.    WATERS QUATTRO PREMIER XE ACQUISITION CONDITIONS USED
             TO COLLECT METHOD PERFORMANCE DATA"
Analyte
ISb: Monochloroacetic acid-2-13C
Monochloroacetic acid
IS: Monobromoacetic acid-7-13C
Monobromoacetic acid
Bromate
Dalapon
IS: Dichloroacetic acid-2-13C
Dichloroacetic acid
Bromochloroacetic acid
Dibromoacetic acid
IS: Trichloroacetic acid-2-13C
Trichloroacetic acid
Bromodichloroacetic acid
Chlorodibromoacetic acid
Tribromoacetic acid
Transition
(m/z)
94/35
93/35
138/79
137/79
127/111
141/97
128/84
127/83
173/129
217/173
162/118
161/117
163/119
163/81
207/79
251/79
Dwell
(seconds)
0.4
1.2
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.0
1.0
1.0
Periods
MRM
Window 1
MRM
Window 2
MRM
Window 3
Cone
(V)
-15
-15
-15
-15
-25
-18
-17
-17
-17
-18
-16
-16
-25
-28
-28
Collision
Energy (V)
-8
-8
-10
-10
-18
-8
-10
-10
-10
-12
-8
-8
-10
-10
-12
   Source block:  120 °C, desolvation gas: 350 °C @ 940 liters/hour, capillary:  -2.8 V, collision pressure:  5.5xlO"3
   torr (0.15 flow @ 7 psig), cone flow:  100 liters/hour, extractor: -3 V, RF lens: -0.5 V, acetonitrile flow rate:  0.2
   mL/min.

   IS = internal standard.
                                           557-31

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TABLE 3.   IC-ESI-MS/MS ANALYTE RETENTION TIMES, PRECURSOR AND PRODUCT
           IONS
Analyte
Monochloroacetic acid
Monobromoacetic acid
Bromate
Dalapon
Dichloroacetic acid
Bromochloroacetic acid
Dibromoacetic acid
Trichloroacetic acid
Trichloroacetic acid (alternate)
Bromodichloroacetic acid
Chlorodibromoacetic acid
Tribromoacetic acid
Retention Time"
(min)
12.62
14.05
14.93
23.33
24.26
26.16
28.89
41.08
42.89
45.50
49.22
Internal Standard
Assignment
MCAA[2-13C]
MBAA[1-13C]
MBAA[1-13C]
DCAA[2-13C]
DCAA[2-13C]
DCAA[2-13C]
DCAA[2-13C]
TCAA[2-13C]
TCAA[2-13C]
TCAA[2-13C]
TCAA[2-13C]
TCAA[2-13C]
Precursor
93
137
127
141
127
173
217
161
163
163
207
251
Product
35
79
111
97
83
129
173
117
119
81
79
79
  Dionex AS24 column (used to collect method performance data).
        TABLE 4. IC-ESI-MS/MS INTERNAL STANDARD RETENTION TIMES,
                 PRECURSOR AND PRODUCT IONS
Internal Standard
Monochloroacetic acid-2-13C
Monobromoacetic acid-7-13C
Dichloroacetic acid-2-13C
Trichloroacetic acid-2-13C
Retention Time
(minutes)
12.56
14.05
24.21
41.08
Precursor
94
138
128
162
Product
35
79
84
118
          Dionex AS24 column (used to collect method performance data).
                                     557-32

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TABLE 5.   IC-ESI-MS/MS LOWEST CONCENTRATION MINIMUM REPORTING LEVEL
            (LCMRL)
Analyte
Monochloroacetic acid


Monobromoacetic acid
Bromate
Dalapon

Dichloroacetic acid
Bromochloroacetic acid


Dibromoacetic acid
Trichloroacetic acid - m/z 163/1 19

Bromodichloroacetic acid
Chlorodibromoacetic acid
Tribromo acetic acid
LCMRL Fortification Levels (ug/L)
0.10, 0.25, 0.375, 0.50, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0

0.050, 0.10, 0.25, 0.375, 0.50, 0.75, 1.0, 1.25, 1.5, 1.75,
2.0
0.025, 0.050, 0.10, 0.25, 0.375, 0.50, 0.75, 1.0, 1.25, 1.5,
1.75,2.0
0.25, 0.375, 0.50, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0
0.025, 0.050, 0.10, 0.25, 0.375, 0.50, 0.75, 1.0, 1.25, 1.5,
1.75,2.0
0.10, 0.25, 0.375, 0.50, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0

0.025, 0.050, 0.10, 0.25, 0.375, 0.50, 0.75, 1.0, 1.25, 1.5,
1.75,2.0
0.10, 0.25, 0.375, 0.50, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0

0.050, 0.10, 0.25, 0.375, 0.50, 0.75, 1.0, 1.25, 1.5, 1.75,
2.0
0.050, 0.10, 0.25, 0.375, 0.50, 0.75, 1.0, 1.25, 1.5, 1.75,
2.0
0.10, 0.25, 0.375, 0.50, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0
Calculated LCMRL
(Hg/L)
0.58


0.19
0.042
0.41

0.13
0.16


0.062
0.25

0.19
0.080
0.27
TABLE 6.   IC-ESI-MS/MS DETECTION LIMITS (DL)a
Analyte
Monochloroacetic acid
Monobromoacetic acid
Bromate
Dalapon
Dichloroacetic acid
Bromochloroacetic acid
Dibromoacetic acid
Trichloroacetic acid - m/z 163/1 19
Bromodichloroacetic acid
Chlorodibromoacetic acid
Tribromoacetic acid
Fortification Level (ug/L)
0.25
0.10
0.025
0.25
0.10
0.25
0.025
0.10
0.050
0.10
0.25
Calculated DL (ug/L)
0.20
0.064
0.020
0.038
0.055
0.11
0.015
0.090
0.050
0.041
0.067
  DLs calculated using data acquired over the course of three days (n=7 sample replicates).
                                       557-33

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TABLE 7.
IC-ESI-MS/MS PRECISION AND ACCURACY OF METHOD ANALYTES
FORTIFIED AT 1.0 AND 15 ug/L IN REAGENT WATER
Analyte
Monochloroacetic acid
Monobromoacetic acid
Bromate
Dalapon
Dichloroacetic acid
Bromochloroacetic acid
Dibromoacetic acid
Trichloroacetic acid - m/z 163/1 19
Bromodichloroacetic acid
Chlorodibromoacetic acid
Tribromoacetic acid
Fortified Cone. = 1.0 ug/L
(n=7)
Mean %
Recovery
101
97.5
93.3
97.4
109
103
104
99.1
105
90.4
101
Relative Standard
Deviation
3.5
3.7
2.4
4.7
2.6
2.9
9.0
2.3
3.7
5.9
5.3
Fortified Cone. = 15 ug/L
(n=8)
Mean %
Recovery
101
99.8
104
100
97.0
107
111
99.8
97.7
103
98.9
Relative Standard
Deviation
1.7
1.8
7.8
3.3
6.5
4.4
6.7
3.2
2 2
5.4
3.0
TABLE 8.
IC-ESI-MS/MS PRECISION AND ACCURACY OF METHOD ANALYTES
FORTIFIED AT 1.0 AND 15 ug/L IN SYNTHETIC SAMPLE MATRIX
Analyte
Monochloroacetic acid
Monobromoacetic acid
Bromate
Dalapon
Dichloroacetic acid
Bromochloroacetic acid
Dibromoacetic acid
Trichloroacetic acid - m/z 163/1 19
Bromodichloroacetic acid
Chlorodibromoacetic acid
Tribromoacetic acid
Fortified Cone. = 1.0 ug/L
(n=8)
Mean %
Recovery
109
97.2
117
113
89.9
84.9
91.0
107
91.6
98.8
94.0
Relative Standard
Deviation
4.8
5.3
11
4.5
9.3
9.3
14
5.4
4.7
7.2
5.4
Fortified Cone. = 15 jig/L
(n=8)
Mean %
Recovery
101
99.7
109
93.2
90.9
82.8
84.5
101
91.0
97.6
97.6
Relative Standard
Deviation
4.1
4.6
11
6.6
8.7
10
10
1.1
4.1
6.2
2.5
                                  557-34

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TABLE 9.
IC-ESI-MS/MS PRECISION AND ACCURACY OF METHOD ANALYTES
FORTIFIED AT 2.5 AND 10 ug/L IN CHLORINATED GROUND WATER3
Analyte
Monochloroacetic acid
Monobromoacetic acid
Bromate
Dalapon
Dichloroacetic acid
Bromochloroacetic acid
Dibromoacetic acid
Trichloroacetic acid - m/z 163/1 19
Bromodichloroacetic acid
Chlorodibromoacetic acid
Tribromoacetic acid
Native
Cone.,
Jlg/L
(n=6)
0.57
0.41
0.56
0.37
4.3
3.4
2.0
2.6
2.6
1.7
0.24
Fortified Cone. = 2.5 ug/L
(n=8)
Mean %
Recovery1"
95.9
101
107
95.5
99.7
95.2
95.2
101
91.2
103
97.6
Relative Standard
Deviation
4.7
2.1
7.3
3.1
6.2
5.6
8.1
1.8
2.0
3.6
1.9
Fortified Cone. = 10 jig/L
(n=8)
Mean %
Recovery1"
99.6
101
102
98.5
106
93.5
99.3
102
99.0
102
95.8
Relative Standard
Deviation
5.2
1.8
4.8
3.0
1.7
3.1
6.2
2.8
3.6
7.2
1.9
   Ground water physical parameters:  pH = 7.45; total hardness = 308 milligrams/liter (mg/L) (as CaC03); free chlorine :
   0.94 mg/L.
   Recoveries corrected for native levels in the unfortified matrix.
TABLE 10.
IC-ESI-MS/MS PRECISION AND ACCURACY OF METHOD ANALYTES
FORTIFIED AT 2.5 AND 8.0 ag/L IN CHLORINATED SURFACE WATER3
Analyte
Monochloroacetic acid
Monobromoacetic acid
Bromate
Dalapon
Dichloroacetic acid
Bromochloroacetic acid
Dibromoacetic acid
Trichloroacetic acid -m/z 163/119
Bromodichloroacetic acid
Chlorodibromoacetic acid
Tribromoacetic acid
Native
Cone.,
Jlg/L
(n=6)
2.6
0.66
0.85
0.72
15
6.4
1.6
11
4.7
1.2
0.081
Fortified Cone. = 2.5 ug/L
(n=8)
Mean %
Recovery1"
97.9
99.3
99.0
97.8
79.6
87.2
106
95.6
99.9
102
99.5
Relative Standard
Deviation
3.5
1.4
8.8
3.8
6.3
9.0
10
2.5
4.6
5.9
3.9
Fortified Cone. = 8.0 ug/L
(n=7)
Mean %
Recovery1"
98.8
101
103
96.3
80.0
90.2
95.8
97.1
97.9
102
103
Relative Standard
Deviation
3.0
1.6
10
4.8
6.0
9.2
6.0
1.4
4.9
11
4.7
   Surface water physical parameters:  pH = 7.43; total hardness = 154 milligrams/liter (mg/L) (as CaC03); free chlorine :
   2.7 mg/L; total chlorine = 3.7 mg/L.
   Recoveries corrected for native levels in the unfortified matrix.
                                             557-35

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TABLE 11.  INITIAL DEMONSTRATION OF CAPABILITY (IDC) QUALITY CONTROL
           REQUIREMENTS
Method
Reference
Section
9.2.1
Section
9.2.1
Section
9.2.2
Section
9.2.3
Section
9.2.4
Section
9.2.5
Requirement
Demonstration of
low system
background
Test for system
carryover
Demonstration of
precision
Demonstration of
accuracy
MRL
confirmation
Quality Control
Sample (QCS)
Specification and Frequency
Analyze a Laboratory Reagent
Blank (LRB) prior to any other
Initial IDC steps.
Analyze an LRB after the high
calibration standard during the IDC
calibration.
Analyze 7 replicate Laboratory
Fortified Blanks (LFBs) and 7
Laboratory Fortified Synthetic
Sample Matrix samples (LFSSMs)
fortified near the midrange
concentration.
Calculate average recovery for
replicates used in Section 9.2.2.
Fortify and analyze 7 replicate LFBs
at the proposed MRL concentration.
Confirm that the Upper Prediction
Interval of Results (PIR) and Lower
PIR (Sect. 9.2.4.2) meet the
recovery criteria.
Analyze mid-level QCS.
Acceptance Criteria
Demonstrate that all method analytes
are  50%
Results must be within +30% of the
true value.
                                   557-36

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TABLE 12.   ONGOING QUALITY CONTROL REQUIREMENTS
Method
Reference
Requirement
Specification and Frequency
Acceptance Criteria
Section
11.3.3
Verify divert
windows
Analyze a Laboratory Fortified
Synthetic Sample Matrix (LFSSM)
prior to each Analysis Batch.
See Section 10.2.5 for acceptance
criteria.
Section
10.3
Initial calibration
Use the internal standard cali-
bration technique to generate a
linear or quadratic calibration
curve.  Use at least five standard
concentrations.  Validate the cali-
bration curve as described in
Section 10.3.3.
When each calibration standard is
calculated as an unknown using the
regression equations, the lowest
level standard must be within +50%
of the true value. All other points
must be within +30% of the true
value.
Section
9.3.1
Laboratory Reagent
Blank (LRB)
Analyze one LRB with each
Analysis Batch.
Demonstrate that all method ana-
lytes are below 1/3 the Minimum
Reporting Level (MRL), and that
possible interference from reagents
and glassware do not prevent identi-
fication and quantitation of method
analytes.
Section
10.4
Continuing Calibra-
tion Check (CCC)
Verify initial calibration by ana-
lyzing a low-level CCC at the
beginning of each Analysis Batch.
Subsequent CCCs are required
after every 10 field samples, and
after the last field sample in a
batch.
The lowest level CCC must be
within+50% of the true value. All
other points must be within +30% of
the true value.

Results for field samples that are not
bracketed by acceptable CCCs are
invalid.
Section
9.3.4
Internal standard (IS)
Isotopically labeled internal
standards are added to all standards
and samples.
Peak area counts for each IS must be
within ±50% of the average peak
areas in the initial calibration.
Section
9.3.5
Laboratory Fortified
Sample Matrix
(LFSM)
Analyze one LFSM per Analysis
Batch. Fortify the LFSM with
method analytes at a concentration
greater than the native
concentrations of most analytes.
Calculate LFSM recoveries.
For LFSMs fortified at concen-
trations <2 x MRL, the result must
be within +50% of the true value.
At concentrations greater than the 2
x MRL, the result must be within
+30% of the true value.
Section
9.3.6
Laboratory Fortified
Sample Matrix Dup-
licate (LFSMD) or
Laboratory Duplicate
(LD)	
Analyze at least one LFSMD or
LD with each Analysis Batch.
For LFSMDs or LDs, relative
percent differences must be <30%.
(<50% if concentration <2 x MRL.)
Section
9.3.7
Quality Control
Sample (QCS)
Analyze mid-level QCS at least
quarterly.
Results must be +30% of the true
value.
                                               557-37

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                                            To Waste
From Suppressor
      Eluent Out
                    Conductivity
                       Cell
                                                              Ports 4, 5, and 6
                                                                are Plugged
                                                                        Position 1 (Divert to Waste)

                                                                        Position 2 (To MS/MS)
                                                                	0.010" PEEK Tubing
Upchurch U-466
Static Mixing Tee
                                                                               To ESI
                                                                               Interface
                                                        Acetonitrile from
                                                        Secondary Pump
                        Figure I. Divert valve placement in sample path.
                                             557-38

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10Ch
                                                                                                                   1.0465
                                                                                                                    Time
            5.00
10.00      15.00      20.00      25.00      30.00     3500
                                           40.00
                          45 HO
50.00      55.00
         Divert
Divert
  cr
       Divert
Carbonate, SO4=, NO3"
                      Figure 2. Dionex AS24 column: procedural calibration standard (5 ug/L).
                                                       557-39

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100n
              MCAA 93/35
                                         Dalapon
                                 ,MBAA
                                                                      TCAA 161/117

                                                                      TCAA 163/119-
                                                              DBA A
                                                                                                                5.0865
                                                 a
                                                                                          BDCAA
                                                                                       j\   ACDBAArTBAA
                                                                                                                 Time
            5.00      10.00   '   15.00      20.00      25.00      30.00     35.00   '   40.00      45.00      50.00
         Divert
Divert
 cr
       Divert
Carbonate, SO4=, NO3"
                             Figure 3. Dionex AS24 column: tap water fortified at 8 ug/L.
                                                      557-40

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100-1
  ss-
                                                      243e4
            MCAA 93/35
                                     MBAA
                                       BrO,
              10 00
                        1200      14.00
                                          1600
                        Area enlarged above
                                         Dalapon
                                                         TCAA 163/119

                                                            TCAA 161/117


                                                                  TCAA
                                                                                            BDCAA
                                                                                                                   2.5865
                                                                                                  CDBAA  ToAA
                                                                                               A       ^-- TBAA
                                                                                                                    Time
            5.00
10.00      15.00
20.00
25.00      30.00      3500      40.00
45.00      50.00
         Divert
                 Divert
                   cr
                               Divert

                        Carbonate, SO4=, NO3"
Figure 4. Dionex AS24 column: synthetic sample matrix fortified at 5 ug/L plus chlorite (1 mg/L) and chlorate (0.5 mg/L).
                                                        557-41

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1 ODD-,
 S30-
 eso-
 •433-
 -33-
                   Area enlarged below
                                                Cl
                                                                          SO/-
52-
53-
   2D3SS:'j HAA#S
23-
 3-
,CIO,
                                              cr
                                                                                      so,
                                                                        Carbonate and
                                                                             CI03:
                                                                                                         NO,
  ! D
              '33    12 3    '-3    If 3    1S 3    23 3
                                        Divert
                                                               2S 3   233   233    323    2" 3    ?e 3    2S 3    ^33    -2 3
                                                                     Divert
                                                                                                                            -; s
  Figure 5. Dionex AS24 column: conductivity trace, synthetic sample matrix plus chlorite (1 mg/L) and chlorate (0.5 mg/L).
                                                            557-42

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