Elemental Analysis Manual

for Food and Related Products

4.7 Inductively Coupled Plasma-Mass Spectrometric

Determination of Arsenic, Cadmium, Chromium,
Lead, Mercury, and Other Elements in Food
Using Microwave Assisted Digestion

Version 1.1 (March 2015)

Current Validation Status: Authors:

AOAC/ASTM: No Patrick J. Gray
SINGLE LAB VALIDATION: YES William R. Mindak
MULTI-LAB VALIDATION: NO John Cheng

GLOSSARY

Table of Contents
4.7 INDUCTIVELY COUPLED PLASMA-MASS SPECTROMETRIC DETERMINATION OF
ARSENIC, CADMIUM, CHROMIUM, LEAD, MERCURY, AND OTHER ELEMENTS IN FOOD USING
MICROWAVE ASSISTED DIGESTION .................................................................................................................1
4.7.1 SCOPE AND APPLICATION .............................................................................................................................2
4.7.2 SUMMARY OF METHOD .................................................................................................................................2
4.7.3 EQUIPMENT AND SUPPLIES ...........................................................................................................................3
4.7.4 REAGENTS AND STANDARDS ........................................................................................................................5
4.7.5 DIGESTION PROCEDURE ................................................................................................................................8
4.7.6 METHOD QUALITY CONTROL ...................................................................................................................... 12
4.7.7 DETERMINATION PROCEDURE..................................................................................................................... 15
4.7.8 CALCULATIONS ........................................................................................................................................... 22
4.7.9 REPORT ....................................................................................................................................................... 23
4.7.10 METHOD VALIDATION ............................................................................................................................ 23
4.7.11 METHOD REVISION HISTORY ................................................................................................................... 24
4.7.12 REFERENCES ...................................................................................................................................... 24
FDA Elemental Analysis Manual (Section 4.7 ICP-MS Method)

4.7.1 SCOPE AND APPLICATION

This method describes procedures for determining total acid-extractable concentrations of

arsenic, cadmium, chromium, copper, lead, manganese, mercury, molybdenum, nickel, selenium
and zinc in food by microwave assisted acid decomposition and inductively coupled plasma-
mass spectrometry (ICP-MS). Other matrices may be analyzed by these procedures if
performance is verified in the matrix of interest, at the concentration levels of interest.
This method should only be used by analysts familiar with trace element analysis and ICP-MS.
The analyst must be trained in the interpretation of spectral and matrix interferences and
procedures for their correction.

4.7.2 SUMMARY OF METHOD

An analytical portion of food is decomposed in acid inside a high-pressure digestion vessel using microwave heating.1, 2
The analytical solution is analyzed using an inductively coupled plasma mass spectrometer (ICP-MS). Elemental
concentrations are quantified using external calibration and quality controls are incorporated to ensure data quality.

4.7 Figure 1 shows the method procedures.

4.7 Figure 1: Procedure flow chart

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Typical analytical limits were calculated per §3.2 and are listed in

4.7 Table 1 but will vary depending on the specific instrumentation, dilution factor and blank
quality. Significantly lower LODs and LOQs have been achieved for a number of target analytes
for different matrices and larger sample masses. Achieving the lowest limits will require
meticulous attention to operating conditions and the highest level of quality control for each set
of analyses.

4.7 Table 1. Nominal Analytical Limits

a a b b
MBKL MBKC ASDL ASQL LOD LOQ
Element Symbol
(µg/kg) (µg/kg) (µg/kg) (µg/kg) (µg/kg) (µg/kg)
52
Chromium Cr 0.0220 0.0546 0.0539 0.489 5.39 48.9
55
Manganese Mn 0.00909 0.0232 0.0233 0.212 2.33 21.2
60
Nickel Ni 0.0205 0.0591 0.0638 0.580 6.38 58.0
65
Copper Cu 0.0215 0.0580 0.0602 0.547 6.02 54.7
66
Zinc Zn 0.0379 0.264 0.374 3.40 37.4 340.
75
Arsenic As 0.00340 0.0111 0.0127 0.116 1.27 11.6
78
Selenium Se 0.0152 0.0592 0.0728 0.661 7.28 66.1
95
Molybdenum Mo 0.0140 0.0454 0.0518 0.471 5.18 47.1
111
Cadmium Cd 0.000635 0.00311 0.00408 0.0371 0.408 3.71
201
Mercury Hg 0.00171 0.00693 0.00861 0.0782 0.861 7.82
sum
Lead Pb 0.00455 0.0118 0.0120 0.109 1.20 10.9
a.
Based upon method blanks measured during the single lab validation over 1 year; n = 143 (see §3.2)
b.
Based upon 0.5 g analytical portion and 50 g analytical solution

4.7.3 EQUIPMENT AND SUPPLIES

Disclaimer: The use of trade names in this method constitutes neither endorsement nor
recommendation by the U. S. Food and Drug Administration. Equivalent performance
may be achievable using apparatus and materials other than those cited here.

(1) Inductively coupled plasma mass spectrometer (ICP-MS)—Capable of scanning mass-

to-charge (m/z) range 5 – 240 amu with a minimum resolution of 0.9 amu at 10% peak
height. Must have collision/reaction cell that can be pressurized with helium and kinetic
energy discrimination for polyatomic interference attenuation. Method was developed
on Agilent™ models 7500ce, 7700x, 7900 and 8800 and directions are specific to
Agilent brand equipment. Use of the method with other brands of instruments or models
may require procedural modifications. Any such modifications must be validated
according to FDA guidelines and method quality control elements (§4.7.6) must pass.6
(2) Microwave digestion system—Requires temperature control to at least 200 °C and
pressures ≥ 300 psi (~ 20 bar) with appropriate safety features to prevent over-
pressurization of vessels. Microwave must have multi-step programming with ramp to
temperature capability. Digestion vessels must be PFA, TFM Teflon® lined or quartz.

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Directions on use of microwave digestion equipment are specific to CEM™ or

Milestone™. Method was developed using CEM MARS Xpress™ and Milestone
UltraWAVE™ and UltraCLAVE™ III systems.
(3) Labware—All laboratory ware must be sufficiently clean for trace metals analysis. The
recommended cleaning procedure for all laboratory ware includes washing with clean-
rinsing laboratory detergent such as Micro-90, reagent water rinse, soaking in 10%
nitric acid and final reagent water rinse. Glass should not be used because of possible
contamination. Labware can be tested for contamination before using a particular lot
with 1% nitric acid. Virgin (non-recycled) Teflon® FEP, PFA, PP, LDPE or HDPE are
recommended materials. Non-metal spatulas should be used for sampling food portions.
(4) Gloves—Use powder free vinyl or nitrile. Do not use powdered or latex gloves because
of possible contamination. Gloves intended for clean rooms and are free from metals
contamination are suggested.
(5) Analytical balance—Capable of measuring to 0.1 mg.
(6) Top Loading balance—Capable of measuring to 0.01 g.
(7) Micropipettes—Air displacement micropipettes with metal free colorless disposable
plastic tips. Do not use colored tips due to possible contamination. If applicable, remove
metal tip ejector to avoid potential contamination.
(8) Clean air hood/canopy—Class 100 polypropylene metal free hoods/canopies are
recommended for sample handling.
(9) Peristaltic pump tubing—Recommended sample and internal standard (ISTD) peristaltic
pump tubing is black:black (0.76 mm inner diameter). At 0.1 rev/s (6 RPM)
approximately 200 L/min sample and 200 L/min ISTD are delivered to the nebulizer
(see 4.7 Figure 2).
a. The 1:1 sample-to-ISTD ratio dilutes the sample 2x inside the mixing tee so that
digests can be diluted to 50 g directly into an autosampler vial.
b. A 1:1 sample-to-ISTD ratio also ensures both sample and ISTD pump tubing
stretch at the same rate over and reduces instrumental drift.
(10) A ~16:1 sample-to-ISTD ratio has been previously used in “Draft Method for Analysis
of Foods for As, Cd, Cr, Hg and Pb by ICP-MS CFSAN/ORS/DBC/CHCB April 25,
2011.” Other pump tubing sizes are acceptable but all QCs must pass to show adequate
performance.
a. Note: EAM 4.7 was validated with 1:1 sample to ISTD mixing. Solution
concentrations and matrices listed assume 1:1 sample-to-ISTD.
b. For 16:1 sample-to-ISTD ratio (Agilent default), the sample pump tubing is
white:white (1.02 mm i.d.) and ISTD is orange:blue (0.25 mm i.d.).
c. If opting for sample-to-ISTD other than 1:1, the following adjustments must be
made:
i. Assume 50% acid consumption during digestion and matrix match
standards to analytical solutions

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ii. Make corresponding adjustments in ISTD and isopropanol concentrations

(11) Drain tubing—Recommended drain tubing is yellow:blue (1.52 mm i.d.) or larger
which drains > 650 L/min from the spray chamber. Smaller drain tubing will result in
spray chamber flooding.

4.7 Figure 2. Recommended peristaltic pump tubing schematic

4.7.4 REAGENTS AND STANDARDS

Use high purity or trace metals grade reagents at all times. Blank levels will be < ASQL if using
best laboratory practices and high purity reagents.

Safety Notes: Reagents should be regarded as potential health hazards and exposure
to these materials should be minimized. Follow universal precautions. Wear gloves, a
lab coat, and safety glasses while handling reagents.

Exercise caution when handling and dispensing concentrated acids. Always add acid
to water. Acids are caustic chemicals that are capable of causing severe eye and skin
damage. If acids or bases come in contact with any part of the body, quickly wash the
affected area with copious quantities of water for at least 15 minutes.

Reagents
(1) Reagent water—Water meeting specifications for ASTM Type-I water3.
(2) Argon supply—High purity (99.99%) argon.
(3) Helium for collision cell—Ultra high purity (99.999%)
(4) High purity nitric acid—Concentrated (67-70%, sp. Gr. 1.42), double distilled. The
trade name for double distilled grade will vary by manufacturer.
(5) High purity hydrochloric acid—Concentrated (30-35%, sp. Gr. 1.18), double distilled.

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(6) High purity isopropanol—Electronic grade or equivalent.

(7) Nitric acid (for cleaning)—Concentrated (sp gr 1.42), trace metals grade.
(8) Hydrogen Peroxide—Concentrated (30%), high purity or trace metals grade.

Solutions
(1) Hydrochloric acid 10% (v/v)—Dilute 200 mL (236 g) high purity HCl to 2,000 mL with
reagent water.
Recommendation: Prepare solution in an empty bottle originally used for
concentrated hydrochloric acid. Dilute gravimetrically on a top loading balance
with a capacity of a least 2500 g. Tare bottle. Fill with approximately 1000 mL
reagent water. Note mass. Add approximately 200 g acid while pouring slowly from
the stock bottle. Add the remaining acid from a Teflon squeeze bottle to enable fine
control of acid addition. The total mass of concentrated hydrochloric acid added
should be 236 g (200 mL * 1.18 g/mL = 236 g). Add reagent water until a total
solution mass of ~2036 g is reached (1800 g water + 236 g HCl). Cap bottle and
mix.
(2) Diluent and rinse solution 5% HNO3 & 0.5% HCl (v/v)—Dilute 100 mL HNO3 (142 g)
and 10 mL (11.8 g) HCl to 2,000 mL with reagent water.
Recommendation: Use an empty bottle originally used for concentrated
hydrochloric or nitric acid. Dilute gravimetrically on a top loading balance with a
capacity of a least 2500 g if making 2L of solution. Tare bottle. Fill with
approximately 1000 g reagent water. Note mass. Add 11.8 g (10 mL) high purity
HCl (double distilled, 30-35%). Swirl to mix. Add 142 g (100 mL) high purity
HNO3 (double distilled, 67-70%). Dilute with reagent water to 2L or ~2044 g. It is
recommended to add concentrated acids either with a high purity bottle top acid
dispenser or Teflon PFA squeeze bottle.
(3) Internal standard solution (ISTD)—Multi-element solution prepared by diluting an
appropriate volume of stock standard. ISTD matrix is 1% HNO3, 0.5% HCl and 4%
isopropanol. The presence of isopropanol will help equalize arsenic and selenium
sensitivities due to residual carbon post digestion.4 The ISTD dilution factor is 1:1 if the
autosampler and internal standard peristaltic pump tubes are equal inner diameter. The
analytical solution pumped into the nebulizer will be approximately 2% isopropanol.
a. ISTD solution may be prepared volumetrically. The exact concentration is not as
important as maintaining the same concentration over an analytical sequence.
b. ISTD elements and suggested concentrations: 20 ng Ge/g, 2.5 ng Rh/g, 5 ng Ir/g,
and 2.5 ng Bi/g. These concentrations are only suggestions. Labs may alter at
their discretion as long as QC passes.
c. If using default Agilent tubing (1.02 mm i.d. sample white/white and 0.25 mm
i.d. orange/blue) then increase IPA and ISTD elemental concentrations
approximately 8x. The exact concentration is not important.

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(4) Recommended Tuning Solution—2 µg/L Li, Co, Y, Ce, and Tl solution in 5% HNO3 –
0.5% HCl used to tune ICP-MS.
The method suggests sample tubing and ISTD tubing to be equal diameter,
diluting tune solution by 2×. Therefore, tune solution should be 2 µg/L so that 1
µg/L is aspirated into the ICP (see 4.7 Figure 2).

Calibration Standard Solutions

(1) Analyte stock standard solutions—Commercially prepared single element traceable
standard solutions in acid matrices prepared specifically for plasma mass spectrometric
analysis should be used. Custom made multi-element solutions may be economically
viable when one considers the time savings they provide.
a. Standards can be purchased on a mass/mass basis to eliminate density correction
factors. If standards are mass/volume then perform a density correction (refer to
EAM §3.4.4 for gravimetric standard solution preparation).
b. Use standard solutions prior to expiration. Solutions may slowly become more
concentrated due to loss of water vapor through the bottle material and
evaporation while the bottle is uncapped.
c. Example of a multi-element custom standard:
 Hg: 1 g/g
 As, Cr, Cd, Ni, Mo, Se, Pb: 10 g/g
 Mn: 50 g/g
 Cu, Zn: 100 g/g
(2) Intermediate standard solutions—Dilute stock standards with 5% HNO3 – 0.5% HCl
diluent. Store in Teflon® FEP, PP or HDPE bottles. Single element standards may be
combined in the same solution to prepare multi-element calibration standard solutions.
a. All calibration standards should be prepared on a mass/mass basis (refer to §3.4.4 for
gravimetric preparation). Standard certificates of analyses often provide density
information.
b. We recommend making an intermediate standard by gravimetrically diluting the
multielement custom standard mix by 100x.
(3) Standard solutions—Dilute intermediate standard with 5% HNO3 – 0.5% HCl to
prepare multi-element working standards. Store in Teflon® FEP, PP or HDPE bottles.
a. Hg concentration should be kept low to minimize memory effects (carryover)
and wash out times. The high standard (level 5 in table 2) is optional, but it is
needed if analytical solution concentrations are higher than the level 4 standard
as might be the case with predatory fish samples. Preferably, the analyst may
further dilute the sample so that the analytical solution concentration falls within
the calibration range. Longer washout times may be needed if there is Hg
carryover. You may place a Au rinse (~1 ppm Au) after samples containing high
Hg to assist washout.

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b. High concentrations of Mn, Cu and Zn are often present in foods compared to

As, Cr, Cd, Pb, Ni, Mo, Se and Hg. Some foods are fortified in Se and will have
high Se levels. The food label will often list Se (or a Se containing compound) as
an ingredient if this is the case.
c. Table 2 is an example of standard concentrations. These may be changed as long
as QC passes and analytical solution concentrations fall within the calibration
range.

4.7 Table 2. Example of calibration curve standard concentrations

Level 5
Level 1 Level 2 Level 3 Level 4
Analyte (ng/g)
(ng/g) (ng/g) (ng/g) (ng/g)
Optional
Hg 0 0.01* 0.1 1.0 2.5
As 0 0.1 1.0 10.0 25.0
Cr 0 0.1 1.0 10.0 25.0
Cd 0 0.1 1.0 10.0 25.0
Ni 0 0.1 1.0 10.0 25.0
Mo 0 0.1 1.0 10.0 25.0
Se 0 0.1 1.0 10.0 25.0
Pb 0 0.1 1.0 10.0 25.0
Mn 0 0.5 5.0 50.0 125.0
Cu 0 1.0 10.0 100.0 250.0
Zn 0 1.0 10.0 100.0 250.0
* This level Hg may be less than instrument LOD.

(4) Standard blank—5% HNO3–0.5% HCl.

(5) Initial calibration verification (ICV)—Dilute an appropriate volume of stock ICV
solution gravimetrically with 5% HNO3–0.5% HCl so analyte concentration will be at
the approximate midpoint of the calibration curve. ICV and calibration standard
solutions should be prepared from different stock solutions (second source).
(6) Continuing calibration verification (CCV)—Use a mid-level standard.

4.7.5 DIGESTION PROCEDURE

Terms and definitions:

(1) A “digestion batch” is defined as digests from a single rotor undergoing the same
digestion program at the same time. For example, a CEM MARS Xpress digestion
batch will have up to 40 vessels in a digestion batch.
(2) An “analytical sequence” is comprised of the analytical solutions analyzed during a
single sequence following instrument tuning and optimization and with one calibration.
An analytical sequence may contain solutions from more than one digestion batch.

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Perform the following operations in a clean environment to reduce contamination. Use an

exhausting hood when working with nitric acid. See §2.3.1 for additional information on
performing microwave digestions.
Food preparation and homogenization procedures are found in §2.1 through §2.2. Elements of
interest (e.g. Cr, Ni, Mo, Co and Fe) may leach from stainless steel and contaminate foods,
especially when foods are acidic or tough to grind. Care should be taken to prevent leaching of
these elements during contact with metallic (stainless steel) equipment. Replace stainless steel
grinding components with titanium or tungsten carbide when possible.

Considerations of acid concentration in analytical solutions: Nitric acid is lost or

consumed during digestion by reaction with an organic sample, high temperature
decomposition and venting as a vapor. HCl is added immediately after digestion to
stabilize Hg.2 Assuming 50% acid consumption during digestion, the final matrix
concentration is 4-5% HNO3 and 0.5% HCl. The ISTD matrix is 1% HNO3 and 0.5%
HCl. Analytical solution and ISTD are combined in a 1:1 ratio inside a mixing tee so
that the final matrix aspirated into the spray chamber is approximately 3% HNO3 and
0.5% HCl with 2% isopropanol (see 4.7 Figure 2). Mixing internal standard at a 1:1
ratio narrows the range of acid concentrations and total dissolved solids introduced
into the plasma.

Digestion Procedure using conventional closed or self-venting vessels

(1) Add a few drops of reagent grade deionized water to each vessel prior to taring to pre-
wet the analytical portion.
(2) A minimum of 2 MBKs must be included in each digestion batch to verify the absence
of contamination that may arise from the vessels. Place MBKs in random vessels.
(3) Weigh analytical portion into clean vessel liner and record analytical portion mass to
the nearest 0.1 mg.
a. For samples of unknown composition limit the dry-mass equivalent of food to no
more than 0.5 g. If maximum pressure attained for this unknown is less than the
vessel limit then a greater mass may be analyzed.
b. Use less than 0.5 g for samples high in salt or fat.
c. Use an analytical portion mass of 5 g for ready to drink beverages and liquids.
An analytical portion of 5 g should not be exceeded even if calculations based on
the food’s energy indicate that a larger portion could be taken.
d. Use 1 g reagent water for method blanks (MBK) and optional fortified method
blanks (FMB).
e. Add 1 g of reagent water with dry foods and CRMs to help control exothermic
reactions.
(4) Add 8.0 mL of high purity nitric acid (11.3 g) to vessel liner, washing down any
material on walls. A bottle top acid dispenser is suggested. Acid should be added drop
wise until it can be established that the sample will not react violently. If foaming or
reaction with the acid is observed, let the vessels sit uncovered in a clean hood until

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reaction subsides. If a clean hood is unavailable, place caps on vessels without pressing
down fully or, if so equipped, cap vessels but loosen the pressure relief nut (with the
safety membrane) to allow pressure to escape. If, however, it appears that excessive
foaming would result in the sample-acid mixture expanding out of the vessel then cap
the vessel and tighten to appropriate torque to prevent loss of sample or acid.
(5) Add 1 mL high purity 30% H2O2 to each vessel. It may be necessary to pre-digest for
more than 20 minutes before adding H2O2 if samples foam excessively.
(6) Seal vessels, apply correct torque to cap (tighten pressure relief nuts if equipped) and
run the digestion program in 4.7 Table 3.

4.7 Table 3. Closed vessel style microwave digestion program

Digestion Programs for CEM MARS XPress™ with 40-
Position Carousel with Ramp to Temperature Feature

Power is applied for the Ramp Time minutes or until Control

Pressure or Control Temperature is met. If Control Pressure or
Control Temperature are met before end of Ramp Time then
program proceeds to Hold Time
Digestion
a
Maximum Power 100% (1600W )
Ramp Time (min) 25
Hold Time (min) 15
Control Temperature (°C) 200
a
Other power level microwaves are acceptable

(7) After vessels have cooled to less than 50 °C move to an exhausting clean hood and vent
excess pressure slowly. Quantitatively transfer digests to a clean container and dilute
digestion solution to approximately 50 g with reagent water followed by 0.5 mL (1.2 g)
high purity HCl (or 5 mL of 10% HCl solution). Add more reagent water for a final
volume of 100 mL and record final analytical solution mass. The mass of a 100 mL 5%
HNO3 – 0.5% HCl analytical solution is approximately 102 g.

Note: Gravimetric dilution is recommended into a trace element free 100 mL

polyethylene or polypropylene bottle. Total dilution factor will be approximately
200 (0.5 g analytical portion to 102 g analytical solution).

Digestion Procedure using microwave autoclave style digestion systems

(1) Add a few drops of reagent grade deionized water to each vessel prior to taring to pre-
wet the analytical portion.
(2) A minimum of 2 MBKs must be included in each digestion batch to verify the absence
of contamination that may arise from the vessels. Place MBKs in random vessels.
(3) Weigh analytical portion into clean vessel liner and record analytical portion mass to

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the nearest 0.1 mg.

a. For samples of unknown composition limit the dry-mass equivalent of food to no
more than 0.5 g.
b. Use less than 0.5 g for samples high in salt or fat.
c. Use an analytical portion mass of 5 g for ready to drink beverages and liquids.
An analytical portion of 5 g should not be exceeded even if calculations based on
the food’s energy indicate that a larger portion could be taken.
d. Use 1 g reagent water for method blanks (MBK) and optional fortified method
blanks (FMB).
e. Add 1 g of reagent water with dry foods and CRMs to help control exothermic
reactions.
(4) Add 5.0 mL (7.1 g) of high purity nitric acid into each vessel, washing down any
material on walls. Acid should be added drop wise until it can be established that the
sample will not react violently. If foaming or reaction with the acid is observed, let the
vessels sit uncovered in a clean hood until reaction subsides.
If it appears that excessive foaming would result in the sample-acid mixture
expanding out of the vessel then the closed vessel system should be used for this
food.
(5) Add 1 mL high purity 30% H2O2 to each vessel. It may be necessary to pre-digest for
more than 20 minutes before adding H2O2 if samples foam excessively.
(6) After the HNO3 and H2O2additions, the analytical portion should be completely wetted
and well-mixed. Soft agitation in an ultrasonic bath may be useful to assist mixing.
A small amount of reagent water may also be added to completely wet the sample
and wash material from the vessel walls.
(7) Fill reaction chamber PFTE liner with manufacturer’s recommended base load.
a. Milestone UltraCLAVE: 300 mL H2O, 30 mL H2O2, and 3 mL H2SO4.
b. Milestone UltraWAVE: 130 mL H2O, 5 mL H2O2, and 2 mL H2SO4.
c. Replace the base load after each digestion cycle.
(8) Cap each vessel and place vessels into vessel rack.
(9) Place vessel rack into microwave, turn on chiller, close reaction chamber, pressurize
chamber with 40 bar N2 or Ar and begin microwave program (4.7 Table 4).

Note: Quartz or TFM vessels are recommended. Ensure that samples are
completely wetted by the acid.

4.7 Table 4. Autoclave Style Microwave Digestion Program

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Digestion Programs for Milestone UltraWAVE™ with 15-Position rack with

Ramp to Temperature Feature
Step Time Status T1 T2 Pressure Power
1 00:30:00 Ramp 250 °C 60 °C 160 bar 1500 W
2 00:15:00 Hold 250 °C 60 °C 160 bar 1500 W
a
Program adapted from Milestone application note UW-17 (fresh food or feed sample)

(10) After the digestion finishes, allow chamber temperature (T1) to cool to 60 °C and
release pressure no faster than 8 bar/min. Effervescence may occur at higher pressure
release rates resulting in sample loss.
(11) Move cooled and depressurized vessels to an exhausting clean hood. Quantitatively
transfer each digest to a clean container and dilute digestion solution to approximately
25 g with reagent water followed by 0.25 mL (0.6 g) high purity HCl (or 2.5 mL of 10%
HCl solution). Dilute with reagent water to approximately 50 g. Record weight of final
analytical solution to nearest 0.01 g.
(12) Assuming 50% oxidative acid consumption, the final matrix composition is 5% HNO3
and 0.5% HCl.

4.7.6 METHOD QUALITY CONTROL

Failure of any of the QC elements described below to meet performance criteria requires
reanalysis of samples analyzed prior to the loss of method control measures. A single element’s
QC failure does not automatically fail other elements. For example, if Zn QC fails but As QC
passes, it is acceptable to report As results.
The following items are common causes of erroneous results and the associated QC items
follow:
 Vessel contamination may be identified when analyzing duplicate analytical portions.
When RPD of two duplicate analytical portions exceeds 20% and concentrations > LOQ,
it is possible that one of the analytical portions has been contaminated. Analyzing
duplicate portions will not indicate if the bulk composite is contaminated.
 Inadequate spectral interference mitigation is identified through measurement of
multiple isotopes. Where possible, EAM 4.7 calls for measurement of two isotopes.
Elemental concentrations calculated from each isotope should agree to within 20% RPD
when concentrations > LOQ. If they do not, this suggests a spectral interference at one of
the isotope m/z and should be further investigated and remedied.
 Matrix effects may cause unwanted enhancement or depression of sample signal.
Internal standards and have been chosen to compensate for matrix effects, but are not
100% assured. Fortified analytical portion and fortified analytical solution QC failure can
indicate a matrix effect. FAPs and FASs do not correct for or indicate spectral
interferences (or indicate a lack thereof).

The following is the minimum number of quality control samples analyzed with each analytical

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sequence:
 2 method blanks (MBKs)
o Minimum of 2 MBKs and concentration of both MBKs are ≤ MBKC. If 3 or more
MBKs are analyzed then at least two-thirds of MBKs are ≤ MBKC (§3.6). MBKs
exceeding MBKC should be uncommon.
o If MBKC has not been established, subtract average MBK if MBK > ASDL as in
§4.7.8.
o If a failure occurs due to contamination, the source of contamination should be
investigated and remedied. One of the most common contamination issues is spot
(microwave vessel) contamination. When spot contamination is suspected, wash
vessels and run a digestion with vessels as MBKs. Place vessels back in the same
rotor position (or label vessels to keep track). Analyze MBKs and find possible
contaminated vessels. Repeat and/or remove contaminated vessels from use.
o If a failure occurs due to polyatomic interference, increase helium flowrate and/or
energy discrimination and reanalyze the entire sequence. If a failure is still
present, vessels should be thoroughly cleaned and new analytical portions must be
digested.
 Stability Check
o Demonstrate instrument stability by analyzing a midrange multi-element standard
containing the analytes (e.g. CCV). Relative standard deviation (RSD) of ion
signals must be ≤10%. If RSD > 10%, determine and correct problem before
standardization. Stability problems are usually related to sample introduction.
 1 certified reference material (CRM)
Match reference material matrix as closely as possible to the food matrix. In-house RMs
are acceptable if no CRM is available and/or the in-house RM is well characterized.
o RM % true value recovery: 80 – 120% when concentrations > LOQ or within
concentration uncertainty (converted to percent relative uncertainty) supplied on
certificate, whichever is greater.
o If acceptable values are not obtained, the analytical solution may be reanalyzed
once. If acceptability is still not met, recalibrate and reanalyze the entire analytical
sequence and/or prepare and digest new analytical portions.
 Analyze duplicate analytical portions at a frequency of 10%. Analyze at least one
duplicate analytical portion of each food sample type and for any foods where non-
homogeneity is a concern. It is highly recommended that duplicate analytical portions are
analyzed for each food sample.
o RPD < 20% for replicate analytical portions when concentration > LOQ (§3.4.5)
o If RPD < 20% is not achieved, reanalyze replicate analytical solutions once. If
acceptable RPD is still not achieved, the source of imprecision should be
investigated and remedied. The entire analytical sequence may need to be
reanalyzed and/or new analytical portions be digested.

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 1 fortified analytical portion (FAP) per sample type. It is recommended that the food
sample analyzed in duplicate also be spiked for FAP.
o FAP % recovery can fail due to inappropriate fortification levels. We recommend
analyzing the food once as a ‘test’ sample and then fortifying at the proper levels
in a subsequent digestion (report only the second analysis result) or b) fortify
duplicate portions at ‘low’ and ‘high’ levels e.g. fortify one portion at ~100 ng/g
and a separate analytical portion at ~500 ng/g.
o FAP preparation: Spike 50-300% of the native elemental concentration into the
digestion vessel with the analytical portion. If the native concentration range is
unknown, spike at a low level standard analytical solution concentration – (i.e.
using 4.7 Table 2 as an example, spike at level 3 calibrant concentration).
o FAP % marginal recovery: 80 – 120%
o If acceptable recovery is not obtained, ensure spike level is appropriate and
reanalyze analytical solution once. If FAP fails again, reanalyze samples that
followed the last acceptable FAP. If FAP fails again, prepare and digest new
analytical portions.
 1 fortified analytical solution (FAS) per sample type. It is recommended that the food
sample analyzed in duplicate also be spiked for FAS.
o FAS preparation: Spike 50-300% of the analytical solution concentration. If the
native concentration range is unknown, spike at a low level standard analytical
solution concentration – (i.e. using 4.7 Table 2 as an example, spike at level 3
calibrant concentration).
 If FAS fails due to inappropriate fortification levels, then a new FAS
solution must be made.
o FAS % marginal recovery: 90 – 110%
o If acceptable recovery is not obtained, ensure spike level is appropriate and
reanalyze analytical solution once. If FAS fails again, reanalyze samples that
followed the last acceptable FAS. If FAS fails again, prepare a new FAS solution.
 Optional fortified method blank
o FMB preparation: Spike approximately 2x ASQL – 8x ASQL
o FMB % marginal recovery: 90 – 110%

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FDA Elemental Analysis Manual (Section 4.7 ICP-MS Method)

4.7.7 DETERMINATION PROCEDURE

Method parameters are listed in 4.7 Table 5. Internal standards help compensate for matrix
effects and instrumental drift.

4.7 Table 5. ICP-MS Isotopes and Measurement Durations

Recommended Minimum
Monitored Recommended Analysis
Element reporting integration
isotopes ISTD isotope Mode
time (sec)
52, 53 103 52
Chromium Cr Rh Cr 0.3 Helium
55 103 55
Manganese Mn Rh Mn 0.1 Helium
60, 62 103 60
Nickel Ni Rh Ni 0.3 Helium
63, 65 103 65
Copper Cu Rh Cu 0.1 Helium
66, 68 103 66
Zinc Zn Rh Zn 0.1 Helium
75 74 75
Arsenic As Ge As 0.5 Helium
78, 82 103 78
Selenium Se Rh Se 0.3 Helium
95, 98 103 95
Molybdenum Mo Rh Mo 0.1 Helium
111, 114 103 111
Cadmium Cd Rh Cd 0.3 Helium
206, 207, 208 209
Lead Pb Bi Sum isotopes 0.1 Helium
201, 202 193 201
Mercury Hg Ir Hg 0.5 Helium
146
Neodymium Nd — 0.1 Helium
147
Samarium Sm — 0.1 Helium
155
Gadolinium Gd — 0.1 Helium
163
Dysprosium Dy — 0.1 Helium
74
Germanium Ge — 0.1 Helium
103
Rhodium Rh — 0.1 Helium
193
Iridium Ir — 0.1 Helium
209
Bismuth Bi — 0.1 Helium

Instrument Setup
(1) See §3.6.1.4 for additional details on ICP-MS.
(2) Perform manufacturer recommended or laboratory start-up procedures.
(3) Program data acquisition method as shown in 4.7 Table 5.
a. Elements that will not be reported may be removed to save time. Ensure that
proper internal standard isotopes are still measured
b. Use spectrum helium mode and kinetic energy discrimination (Agilent specific
nomenclature – other manufacturers will have different names)
c. Reaction gases are not allowed

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d. Program the autosampler probe to go to the rinse station for at least 10 seconds
after analyzing an analytical solution and then to a rinse bottle. Multiple (3) rinse
bottles are recommended. The rinse time must be great enough so that a standard
blank solution analyzed after the highest standard results in all analytes <ASQL
e. An “intelligent rinse” or “smart rinse” feature may be used if so equipped
Analyte levels must return to within 10% RPD of the average CCB before
moving to the next analytical solution
f. Use 3 points per peak and at least 3 replicates for integration. Use the mean of
the integrations for reporting
(4) Optimize instrument
a. Tune instrument according to the guidelines in the manufacturer’s tuning guide.
The instrument must exceed minimum manufacturer specifications.

Note: During tuning, the internal standard tubing is placed in reagent water.

b. HCl is added to the tuning solution to create chloride based interferences that
would be found in food samples high in salt.
c. Use at least 3 (typically 3 – 4) volts energy discrimination (difference between
octapole and quadrupole biases) and at least 3 (typically 3 – 5) mL/min He flow
rate. Higher He flow rate is allowable and recommended when analyzing ultra-
trace concentrations (< 10 ng/g) of isotopes that suffer from severe polyatomic
interferences such as 52Cr.
e. Keep a record of instrument parameters such as sample gas flow rate, sensitivity,
oxide formation, doubly charged ratio, and stability (count rate %RSD).
(5) Set up method interference correction equations. These equations can also be edited
after data has been acquired.
a. 3 Pb isotopes are summed to account for isotopic variations between standards
and samples. Use the method edit function to sum Pb isotopes.
i. 208: (206)*1 + (207)*1 + (208)*1
74
b. Ge has an isobaric interference with 74Se, which is especially problematic in a
selenium fortified dietary supplement or other selenium fortified food. The Ge
concentration in the ISTD should be high enough that an correction for 74Se on
74
Ge is unnecessary, but an analyst may choose to use 72Ge or 103Rh for high
selenium products.
78
c. Se has an isobaric interference with 78Kr. The Kr isotope is minor abundance but
is occasionally found as an argon impurity. Analysts may use a mathematical
correction for the Kr overlap of Se. Correction factors are calculated from the
natural abundance of Kr and do not incorporate mass bias factors.
i. 78: (78)*1 - (83)*0.031
ii. 82: (82)*1 - (83)*1.008

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d. Interference equations for double charged Nd and Sm must be applied to 75As if

Nd or Sm is present at concentrations high enough to cause a signal greater than
the detection limit at m/z 75 due to Nd++ or Sm++
i. If interference from Nd and/or Sm is suspected from the pre-analysis scan,
analyze 10 ng/g Nd and Sm single element solutions separately.
ii. Calculate the Nd and Sm correction factors from the ratio of the Nd++ and
Sm++ signals at m/z 75 to the 146Nd+ and 147Sm+ signals at their nominal
mass.
iii. Enter these correction factors on 75As using the Method Edit function.
74
iv. Ge is interfered by both 148Nd and 148Sm. The Ge concentration in the
ISTD should be high enough that an interference correction for 74Ge is
unnecessary, but an analyst may choose to enter a correction factor on
74
Ge in the same way as 75As.
e. Interference equations for double charged Gd and Dy must be applied to 78Se if
Gd or Dy is present at concentrations high enough to cause a signal greater than
the detection limit at m/z 78 due to Gd++ or Dy++
i. If interference from Gd and/or Dy is suspected from the pre-analysis scan,
analyze 10 ng/g Gd and Dy single element solutions separately.
ii. Calculate the Gd and Dy correction factors from the ratio of the Gd++ and
Dy++ signals at m/z 78 to the 155Gd+ and 163Dy+ signals at their nominal
mass.
iii. Enter these correction factors on 78Se using the Method Edit function.

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4.7 Table 6. Possible interferences

m/z Element Polyatomic Interferences Elemental Interferences

Analyte Isotopes
52 35 16 40 12 36 16 37 15 34 18 104 ++ 104 ++
Cl OH, Ar C, Ar O, Cl N S O Pd , Ru
Cr
53 37 16 38 15 38 14 36 16 40 13 106 ++ 106 ++
Cl O, Ar N, Ar NH, Ar OH, Ar C Pd , Cd
55 Mn 40 15 40 14 39 16 38 16 110 ++
Ar N, Ar NH, K O, Ar OH Cd
60 44 16 23 37 43 16 120 ++ 120 ++
Ca O, Na Cl, Ca OH Sn , Te
Ni
62 46 16 23 39 46 16 124 ++ 124 ++ 124 ++
Ti O, Na K, Ca O Te , Sn , Xe
63 31 16 40 23 47 16 23 40 46 16 126 ++ 126 ++
P O2, Ar Na, Ti O, Na Ca, Ca OH Te , Xe
Cu
65 49 16 32 16 40 25 40 16 36 14 130 ++ 130 ++ 130 ++
Ti O, S O2H, Ar Mg, Ca OH, Ar N2H Te , Xe , Ba
66 50 16 34 16 33 16 1 32 16 18 32 17 132 ++ 132 ++
Ti O, S O2, S O2 H, S O O, S O2 Xe , Ba
Zn
68 36 16 + 34 16 18 + 40 14 + 35 16 17 + 34 136 ++ 136 ++ 136 ++
S O2 , S O O, Ar N2 , Cl O O , S2 Ba , Xe , Ce
75 As 40 35 59 16 36 38 38 37 36 39 150 ++ 150 ++
Ar Cl, Co O, Ar ArH, Ar Cl, Ar K Sm , Nd
78 38 40 62 16 78 156 ++ 156 ++
Ar Ar, Ni O Kr, Gd , Dy
Se
82 40 66 16 82 164 ++ 164 ++
Ar2H2, Zn O Kr, Dy , Er
95 79 16
Br O
Mo
98 82 16 82 16 98
Kr O, Se O Ru
111 95 16 94 16 39 16
Mo O, Zr OH, K2 O2H
Cd
114 98 16 98 16 114
Mo O, Ru O Sn
201
Hg
202 186 16
W O
206 190 16
Pt O
207 Pb 191 16
Ir O
208 192 16
Pt O
ISTD Isotopes
74 Ge 34 40 37 37 58 16 58 16 74 148 ++ 148 ++
S Ar, Cl Cl, Fe O, NI O Se, Nd , Sm
103 Rh 63 40 87 16 206 ++
Cu Ar, Sr O Pb
193 Ir 177 16
Hf O
209 Bi 193 16
Ir O

Optional Pre-Analysis Scan

An optional pre-analysis scan checks for the presence of ISTD elements and high levels of
analyte which will require additional dilutions.
(1) Analyze analytical solutions (one replicate from each sample) in semi-quant or raw
counts mode. Use 1% HNO3 for ISTD uptake.
(2) ISTD levels are considered significant if the counts in the analytical solution contribute
≥ 2% of the counts in an analytical solution for an ISTD isotope.

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FDA Elemental Analysis Manual (Section 4.7 ICP-MS Method)

a. Use a different ISTD isotope if ISTD is present in analytical solution at a

significant level.
b. If recommended ISTD isotopes cannot be used, optional ISTD isotopes are listed
in 4.7 Table 7.
(3) Some foods may contain tungsten which can interfere with 202Hg via 186W16O. The
absence of W must be confirmed if 202Hg is used.
4.7 Table 7. Optional internal standard isotopes

Recommended Optional
ISTD ISTD
103 105 74
Rh Pd, Ge
74 72 105
Ge Ge, Pd
209 205 175
Bi Tl, Lu
193 195 197
Ir Pt, Au

Determination of Analyte Concentration Using External Standard Calibration Curve

An example of an analytical sequence is shown in 4.7 Table 8.
(1) Calibrate using the standard blank and at least 3 multi-element standards.
(2) Include the calibration blank as a point on the calibration curve (0 g/kg calibrant)
(3) Ignore y-intercept
(4) Both un-weighted and weighted linear regressions are acceptable as long as QC passes.
1/x2 and 1/(st. dev)2 weighted regressions often work well for samples with
concentrations towards the bottom of the calibration range.
(5) Check Standardization Performance
a. Linear regression correlation coefficient (r) must be ≥ 0.9975.
b. Analyze initial calibration verification (ICV) solution to verify standardization.
Recovery must be 100 ± 10% to proceed. If ICV fails, reanalyze one time. If ICV
fails again, determine source of problem and remedy before proceeding.
(6) Check Instrument Measurement Performance and Analyze Analytical Solutions
a. Analyze the highest standard, standard blank and ICV in this order. This order
will show whether the rinse time is adequate.
b. Continuing calibration verification solution (CCV) must be analyzed at a
frequency of 10% and at the end of the analytical sequence. Recovery must be
100 ± 10% to proceed. If CCV fails, reanalyze one time. If CCV fails again,
reanalyze samples analyzed after the last acceptable CCV. If CCV fails a third
time, restart analytical sequence and/or prepare new digests, standards, and QC
solutions.

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c. RSD of replicate integrations must be ≤ 10% for all solutions when instrument
response > 5 times ASQL or greater than 5,000 cps, whichever is greater. If RSD
exceeds 10%, determine source of noise and remedy before proceeding.
d. Continuing calibration blank (CCB) analyzed at a frequency of 10% and at the
end of the analytical sequence and must be < ASQL to proceed. If CCB fails,
reanalyze one time. If CCB fails again, reanalyze samples analyzed after the last
acceptable CCB. If CCB fails a third time, restart analytical sequence with a
longer washout time and/or prepare new digests, standards and QC solutions.
e. Analytical solution concentrations must be less than the highest standard
concentration. Gravimetrically dilute analytical solution if necessary.
(7) Suppression or enhancement of ISTD response may indicate a matrix effect is present.
Monitor internal standard signals and dilute any analytical solution where the internal
standard signal differs by more than 40% from the standard blank.
a. It is helpful to monitor 13C as an ISTD element. Carbon enhanced ionization can
cause false positives of high ionization potential isotopes. Use 13C as an easy
proxy to determine if samples may need further dilution due to high carbon
content (e.g. greater than 200% 13C vs standard blank).
b. In the same way as 13C, monitor 37Cl as an ISTD element. Foods high in salt
(NaCl) may form Cl-containing polyatomic interferences (see table 6).
Determination of Analyte Concentration Using Standard Additions
Quantification by the method of standard additions can also be used.
(1) Analyze 3 additional portions of analytical solution with added varying amounts of
analyte.
(2) Additions should be no less than 0.5 and no greater than 3 times native amount.
(3) Correlation coefficient (r) of linear regression must be ≥ 0.9975. If correlation
coefficient is < 0.9975, repeat analysis. If repeat analysis still fails to meet control limits
then dilute sample by a factor of 2 and re-analyze using additions based on the level in
analytical solution and the dilution factor.

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4.7 Table 8. Analytical Sequence Example

Grouping Solution QC Criteria
+ ++
tune report sensitivity, RSD, MO , M
stability check ≤10% RSD
calibration standards r ≥ 0.9975
standard blank IDL check
high standard solution memory check
standard blank ≤ASQL
ICV 90% - 110% recovery
MBK 1 ≤MBKC
2/3 of MBKs
MBK 2 ≤MBKC
≤MBKC
MBK 3 ≤MBKC
RM 80% - 120% recovery
FMB (optional) 90% - 110% recovery
sample 1 ≤10% RSD, < high cal. std
sample 1 duplicate ≤20% RPD
sample 1 FAS 90% - 110% recovery
sample 1 FAP 80% - 120% recovery
Unknowns - sample 2
Set 1 sample 3
sample 4
sample 5
sample 6
sample 7
CCV 90% - 110%
CCB ≤ ASQL
sample 8 ≤10% RSD, < high cal. std
sample 8 duplicate ≤20% RPD
sample 8 FAS (optional)
sample 8 FAP (optional)
sample 9
Unknowns -
Set 2 sample 10
sample 11
sample 12
sample 13
sample 14
CCV 90% - 110%
CCB ≤ ASQL
Precision required: All solutions must be ≤10% RSD when analyte ≥5xASQL.

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4.7.8 CALCULATIONS

Calculate the concentration (mass fraction) of the analyte in the analytical portion according to:
𝜇𝑔 𝑀
𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 ( ⁄𝑘𝑔) = [(𝑆 × 𝐷𝐹) − 𝑀𝐵𝐾𝐿 ] ×
𝑚 × 𝑀𝐶𝐹

where:
𝑆 = concentration of analyte in analytical solution (or diluted analytical
solution) (ng/g)
𝑀𝐵𝐾𝐿 = laboratory MBK (ng/g) (subtract if average of the three MBK is greater than
ASDL)†
𝑀 = Mass (g) of analytical solution (usually 50 – 100 g)
𝑚 = mass of analytical portion (g)
𝐷𝐹 = dilution factor (1 if analytical solution not diluted)
𝑀𝐶𝐹 = mass correction factor (1 if no water or other solvent was added to aid
homogenization)
Report concentration to no more than 3 significant figures. Concentration may be converted to
other convenient units (e.g., mg/kg, ng/kg for solids or ng/L for liquids providing that the
specific gravity is known).
† MBKL subtraction may not be appropriate for all analyses or labs (i.e. when MBKL is not well
established or when multiple analysts work on a single analytical portion). In this case replace
MBKL in the above equation with the average MBK concentrations from the digestion batch
when MBK > ASDL.

Marginal spike recoveries are calculated as follows:

𝐶𝑥+𝑠 − 𝐶𝑥
% 𝑅𝑒𝑐𝑜𝑣𝑒𝑟𝑦 = [ ] × 100
𝐶𝑠 𝑀𝑠
( 𝑀 )
𝑥
where:
𝐶𝑥+𝑠 = concentration determined in spiked sample (g/kg)
𝐶𝑥 = concentration determined in unspiked sample (g/kg)
𝐶𝑠 = concentration of spiking solution (g/kg)
𝑀𝑠 = mass of spiking solution added to analytical portion (g)
𝑀𝑥 = mass of analytical portion (g)

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4.7.9 REPORT

Report results after all quality control criteria for an analytical sequence have been met. Report
average concentration when replicate analytical portions are analyzed.
 Report results that are ≥LOQ as concentration followed by the units of measurement.
 Report results that are ≥LOD and <LOQ as concentration followed by the units of
measurement and the “Trace” data qualifier that indicates analyte is present at a trace
level that is below the limit of reliable quantification. Trace values are documented by a
“TR” after the result.
 Report results that are <LOD as 0 followed by the units of measurement and the qualifier
that indicates analyte is below the level of reliable detection or is not detected (ND).

Example: LOQ = 10 µg/kg; LOD =3 µg/kg. Levels found for three different
samples were 10 µg/kg, 5 µg/kg and 2 µg/kg.

10 µg/kg is ≥LOQ; report 10 µg/kg

5 µg/kg is ≥LOD but also <LOQ; report 5 µg/kg (TR)

2 µg/kg is <LOD; report 0 µg/kg (ND)

4.7.10 METHOD VALIDATION

In-house validation.
EAM 4.7 has undergone a level 2 single lab validation (SLV) as described in FDA’s Guidelines
for the Validation of Chemical Methods for the FDA Foods Program (Office of Foods and
Veterinary Medicine).6 The cumulative LODs and LOQs for method blanks measured over the
course of 1 year during the SLV (n = 143) are listed in table 1 and are adequate for the intended
purpose of this method. All quality control criteria were followed and met during the SLV.
Analyses were performed on 25 different foods that were similar to those collected in FDA’s
Total Diet Study but purchased from local grocers. Foods were analyzed several (N ≥ 5) times.
Fortified analytical portions (3 spike levels each) were also prepared and analyzed. Repeatability
and reproducibility of the method was < 20% relative standard deviation for elements with
concentrations > LOQ. Fortification and reference material recoveries were in the range of 80-
120%.

Uncertainty.
A result above LOQ has an estimated combined uncertainty of 10%. Use of a coverage factor of
2 to give an expanded uncertainty at about 95% confidence corresponds with the RM recovery
control limit of ± 20%. A result above LOD but below LOQ is considered qualitative and is not
reported with an uncertainty.
A more detailed discussion of method uncertainty is presented in §3.3. This method conforms to

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the information contained in that discussion.

Interlaboratory trial.
A mutli-laboratory validation is currently underway. An updated method will be published with
the multi-lab validation results when the exercise is complete.

4.7.11 METHOD REVISION HISTORY

4.7 Table 9. Method revision history

Version Revisions Made Effective Date
1.0 Method approved and single lab validation completed November 2013
1.1 Revised LOD/LOQ table, added selenium, weighted calibration allowed, February 2015
expanded allowable fortification levels, lowered recommended ISTD
concentrations

4.7.12 REFERENCES
(1) Link, D., Walter, P., and Kingston, H. (1998) Development and Validation of the New EPA Microwave
Assisted Leach Method 3051A, Environ. Sci. Technol. 32, 3628-3632.
(2) U.S. Environmental Protection Agency (2007) SW-846 EPA Method 6020A rev. 1: Inductively Coupled
Plasma-Mass Spectrometry. Available from EPA
(3) ASTM International (2006) ASTM D 1193-06, Standard Specification for Reagent Water. Available from
ASTM
(4) Larsen, E., and Sturup, S. (1994) Carbon-enhanced Inductively Coupled Plasma Mass Spectrometric
Detection of Arsenic and Its Application to Arsenic Speciation, J. Anal. At. Spectrom. 9, 1101-1105.
(5) Official Methods of Analysis of AOAC INTERNATIONAL (2005) 18 th Ed., AOAC International,
Gaithersburg MD, USA, Appendix D: Guidelines for Collaborative Procedures To Validate Characteristics
of a Method of Analysis.
(6) U.S. Food and Drug Administration (2012) Guidelines for the Validation of Chemical Methods for the
FDA Foods Program, Version 1. Available from FDA
.

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