2021.04.07_CCO.p14_DEQGuidelinesForSubmittalOfReferenceMaterialAndModifiedMethods

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April 7, 2021

Guidance for Submittal of Reference Materials and Modified Analytical Chemistry Methods

Overview: This document describes the material and information Chemours should submit to DEQ for
reference materials and modified analytical chemistry methods. Reference materials are chemicals
generated by Chemours that are provided to DEQ and others in solid or liquid form to be used in the
preparation of analytical standards. Certificates of Analysis (CoA) and Safety Data Sheets (SDSs) should
be provided for each reference material. Each batch (or lot) of material should be clearly labeled and
traceable and have a separate CoA. Modified analytical methods are any analytical method used for
PFAS analysis that are not one of these EPA Methods: 537, 537.1, 533, or SW-846 Method 8327. An EPA
Method must be followed exactly, otherwise it is considered a modified method. When a modified
method is used, method documentation should be provided as described below and method codes
should be obtained from DEQ for submitting electronic data deliverables (EDDs).

CoA and SDS
CoAs and SDSs should be provided with each container of reference material. Each batch/lot of
reference material should be separately evaluated for identity, purity, and concentration. CoA and SDS
should ideally be prepared according to good practices using guidance from the International
Organization for Standardization (ISO) and Globally Harmonized System (GHS) standards, respectively.
At a minimum, the CoA should provide information to 1) allow a user to identify what the material
consists of and 2) accurately and with confidence prepare standard solutions of known concentration.
Information that should be included on a CoA is outlined on Page 3 of this document. Analytical data
that should be collected for purity determination is described on page 4 of this document. The SDS
should include any known human health and environmental hazard classifications. Corresponding
hazard symbols should be placed on containers of material provided to ensure the safety of laboratory
personnel.

Modified Analytical Methods
Additional documentation is required when using an analytical method other than EPA Method 537,
537.1, 533, or SW-846 Method 8327. Obtain an unredacted SOP from the lab conducting the analysis.
Identify one the EPA Methods mentioned above that most closely resembles the analytical method used
by the lab. Refer to your method as a modified version of that EPA method. Create a table that
documents each deviation from the EPA method, including all changes to sample preparation, sample
analysis, and QC procedures. See the example reference table of method modifications on the following
page.

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Reference Table of Method Modifications.
This example is for format only and may not reflect the need to document a much longer list of
modifications. However, all modifications made should be included in the comparison table. Use a
sufficient number of rows to capture all changes.
Modified Step EPA Method 537.1 Modified 537.1 version A
Sample collection/preservation 250ml polyethylene bottles
preserved with Trizma.
250ml polyethylene bottles -
only preserved with Trizma if
from a finished chlorinated
water source.
Calibration Model Internal Standard Isotope Dilution
Method Blank/Lab Reagent
Blank
No target analytes above the
MDL which is greater than 1/3
the MRL.
No target analytes above the
reporting limit.

In order to submit EDDs, you will need to obtain electronic codes that correspond to your sample
preparation method and sample analysis method. When a documented method SOP covers both
procedures, the same codes can be input for preparation method and analysis method. Send the
following items to the NCDEQ EQuIS team and copy the DEQ contact receiving the data.
Be sure that all items below to be submitted are for the current samples whose data is being submitted
as an EDD, as the items can change from one sample analysis to the next.
• Unredacted laboratory SOP for methods.

• Reference table of method modifications.

• Name of modified sample prep method and/or modified sample analysis method.

• List of analytes to be tested at the lab along with their CAS numbers. If the chemical is charged,
the lab should refer to the chemical name and CAS number for analyte using the acid or base
version, not the corresponding salt.

EDDs
The NCDEQ EQuIS team will review the information submitted and provide unique method codes to use
for submitting EDDs. Analytes and CAS numbers will be reviewed and added to the approved list of
parameter valid values. A summary of materials to be submitted for modified analytical methods and
for reference materials are below:
• For analytical methods other than one of the EPA Methods previously listed (including
modifications of these EPA methods), submit the following: reference table of method
modification(s), unredacted SOP, method name, and analytes.
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• For Chemours-generated reference materials, submit the following: CoA, SDS, list of possible
EPA analytical methods to use (choose from 537, 537.1, 533, 8327 or modified method with
supporting documents described above).

Information to Provide on a Certificate of Analysis

• Chemical name (ex. Perfluoro-4-oxapentanoic acid)

• Molecular formula (ex. C4HF7O3)

• CAS number (ex. 377-73-1).

• Lot number (ex. PF4OPeA0320)

• Preparation and Expiration dates (ex. 03/31/2025)

• QA/QC reviewer sign off on the certification of the compound

• Identity, purity and concentration characterized by LC/MS/MS, 19F-NMR, and 1H NMR. See the
last page of this document for more details on specific purity data to collect for a CoA. Date of
testing, retest date, and supporting documentation (LC/MS/MS chromatograms, mass spectra,
NMR spectra) should be provided.

• Solubility (ex. Methanol, Water less than 1%)

• Solid materials require the following additional information:
o Physical description of material (ex. crystalline, white powder, yellow powder)
o Important physical characteristics about the solid (ex. hygroscopic)
o Form of chemical present—state all that are applicable (ex. free acid, free base,
ammonium (or other) salt, ·2H2O, stabilizing agents added to solid)
o Moisture content as determined by Karl Fischer titration or loss on drying

• Standard solutions require the following additional information:
o Concentration of compound in solution (ex. 50.0 µg/ml)
o Uncertainty with concentration calculation (ex. ±2.5 µg/ml)
o Solvent in which the compound is dissolved
o Chemical additives in solution (ex. 4 mole eq of NaOH to prevent conversion of the
carboxylic acid to the methyl ester)

• Storage conditions including any temperature, light, and humidity sensitivity considerations.

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Analytical Data to Collect for Certificates of Analysis

Summary: Purity assessment for certificates of analysis (CoAs) should be determined by at least two
analytical methods (LC/MS/MS and NMR). Specific data should be collected for each analytical
technique and is described below.

LC/MS/MS: Obtain several scans of the analyte, including the following (provide chromatograms and
spectra for each):
• Full scan LC/MS data over a mass range from m/z 50 to a m/z that is 50 higher than two times
the expected precursor ion m/z. Provide spectral views that are both zoomed out to show all
m/z values and zoomed in on area(s) showing fragment ions.
• SIM Scan showing precursor compound peak and spectra
• LC/MS/MS full scan data showing the three most abundant optimized product ions using the
optimized precursor compound m/z as the precursor ion and a product ion mass range from a
m/z of 50 to the m/z of the precursor ion. Provide spectral views that are both zoomed out and
zoomed in on the three peaks (four spectra total).
• LC/MS/MS MRM data for the most abundant fragment ions (such that the most abundant
fragment ion MRM has an intensity of 106 in the chromatogram)

NMR: Collect 19F NMR data to look for fluorinated impurities and 1H NMR data to look for non-
fluorinated impurities. For each type of NMR analysis, data should be collected as follows:
• Qualitative assessment to confirm structure (including whether linear or branched). NMR
analysis should be done with sufficiently long pre-delay time (or relaxation time), especially for
1H NMR (30s to 60s)
• Concentration of analyte sufficient to see any impurities present in the standard at 0.1%
• Generate a calibration curve by analyzing the standard solution undiluted and diluted at several
concentrations (ex. 2x, 4x, 8x) to ensure that calculated analyte concentrations are in the
compound-specific linear range of the instrument

Moisture determination: Water content should be determined for solid reference materials. Karl
Fischer titration is the preferred method for moisture determination; however a loss on drying analysis
is also acceptable for moisture determination.