(Certified) Reference Materials
Ioannis Papadakis
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Index
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definitions - documentation
types of (C)RMs
production of (C)RMs
selection and use of (C)RMs
CRMs and traceability
suppliers/producers of (C)RMs
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
ISO Guides
 ISO 30 (1992) terms and definitions used in
connection with RMs
 ISO 31 (2000) certificates of RMs
 ISO 32 (1997) calibration in analytical
chemistry and use of CRMs
 ISO 33 (2000) uses of CRMs
 ISO 34 (2000) general requirements for the
competence of RM producers
 ISO 35 (1989) certification of RMs
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Reference Material
Definition
material or substance one or more of
whose property values are sufficiently
homogeneous and well established to be
used for the calibration of an apparatus,
the assessment of a measurement
method, or for assigning values to
materials
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Reference Material (RM)
 a reference material may be in the form
of a pure or mixed gas, liquid or solid
 examples are water for the calibration of
viscometers, sapphire as a heatcapacity calibrant in calorimetry, and
solutions used for calibration in
chemical analysis
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Certified Reference Material
Definition
reference material, accompanied by a
certificate, one or more of whose property
values are certified by a procedure which
establishes traceability to an accurate
realisation of the unit in which the
property values are expressed, and for
which each certified value is accompanied
by an uncertainty at a stated level of
confidence
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Certified Reference Material
(CRM)
 all CRMs lie within the definition of
“measurement standards” or “etalons”
 CRMs are generally prepared in
batches for which the property values
are determined within stated uncertainty
limits by measurements on samples
representative of the whole batch
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Classification of RMs
 physical character
 gases, liquids or solids
 supplied property
 pure chemical species, physico-chemical property
 preparation method
 synthetic mixtures, natural materials
 metrological qualification
 primary RM, secondary RM
 intended use
 calibration of instruments, validation of analytical methods
Reference Materials in Analytical Chemistry - A Guide for Selection and Use, edited
by A Zschunke, Springer, 2000
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
CRM Production
According to ISO-35
 producing a CRM is:
 the integrated process of correct
preparation, homogeneity and stability
demonstration, and accurate and traceable
characterisation,
 whereby all components of uncertainty of
“the sample on the desk of the user”
should be properly accounted for according
to the ISO-GUM (Guide for the expression of
uncertainty in measurement)
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
CRM Production
Non-trivial Job!
 it requires ...
 skills and installation to process the
material in a suitable form, especially for
matrix CRMs
(e.g. making 2000 containers of orange juice sample for
heavy metals content measurement, with demonstrated
homogeneity and stability)
 demonstrated measurement capability, to
produce reference value
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
CRM Production
Production Process
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select the material
prepare the units (e.g. bottles)
labelling
measure homogeneity
measure stability
assignment of reference values
distribution/marketing
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Select the Material
 depends on the needs of the
analytical community
 measurement that needs to be
supported
 depends on availability of material
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Prepare the Units
 select appropriate container
(size, shape, material, properties …)
 prepare the units (e.g. vials) under the
appropriate conditions
 each unit should contain the appropriate
amount of material
 prepare appropriate number of units
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Measure Homogeneity
 fast measurement method
 small sample quantity
 good reproducibility
 within containers
 between containers
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Measure Stability
 fast measurement method
 small sample quantity
 good reproducibility
 different storing temperatures
 different times
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Assignment of Reference Value
 by measurement (CRM)
 by designation (RM)
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Assignment of Reference Value
by Measurement
 one method in one lab
(e.g. a primary method)
 one method in several labs
 several methods in several labs
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Traceability of the Assigned
Value
 needs to be stated
 … and demonstrated
 information available in
certification report
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Uncertainty of the Assigned
Value (UCRM)
UCRM uncertainty of the average concentration of
1 unit (of the n prepared) after storage for time
T and after transport
UCRM [%]=k*(u2assign+u2bb+u2lts+u2sts)1/2
uassign uncertainty value assignment measurement
ubb uncertainty bottle to bottle variation
ults uncertainty long term stability
usts uncertainty short term stability (transport)
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Labelling
 equally important
 clear and concise
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Distribution / Marketing
 certification report
 appropriate price
 appropriate delivery
 appropriate storage
 reach scientific community
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
In General High Quality CRMs
Should…
 state traceability of certified value
(e.g. traceability to S.I., or to values obtained with method XYZ)
 state an ISO-GUM uncertainty of certified
value
 demonstrate traceability & uncertainty
of certified value
(e.g. in a certification report; experimental evidence of
demonstrated capability from participation to international
comparisons)
 preferably be produced according to the
guidelines of ISO-35
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Use of CRMs
 (ideally) supplier should give advice
 storage temperature
 influence of moisture on long term
stability (e.g. biological activity)
 influence of contamination
 possibility to divide in different portions
after opening
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Use of CRMs
how can CRMs help my measurements?
 calibration (?)
 validation (?)
 measurement control (?)
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
response
Calibration
concentration
use as a matrix matched calibrant
(direct or via working standards)
to ensure traceability of results
to an external reference (the CRM)
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
certified concentration
Concentration
Validation
check the measurement results
in terms of validity:
is there any method specific bias ?
is there any systematic error ?
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Measurement Control
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1
(Upper) Control line
(Upper) Warning line
-1s
0
1s
2s
3s
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
-2s
(i.e. of proven homogeneity
and stability; sometimes
named in-house RMs or
laboratory RMs)
-3s
 Abuse of CRM
 Instead : use inhouse materials or
quality control
materials
(Lower) Warning line
(Lower) Control line
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Use of CRMs
how can CRMs help my measurements?
 calibration (?)
X YES
 validation (?)
X YES
 measurement control (?)
X NO
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
How CRMs are Used in Terms of
Traceability?
S.I.
to calibrate own
analytical instrument
value 1
value 2
my result
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
How CRMs are Used in Terms of
Traceability?
S.I.
value 1
to validate own
analytical method
value 2
my result
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
value CRM
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Selection of CRMs
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availability (problem with matrix CRMs)
concentration range of certified property
uncertainty of certified property
traceability of certified property
what is your uncertainty requirement
contribution of CRM uncertainty on your
measurement uncertainty
 demonstrated competence of CRM producer
 CRM matrix
 cost
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
CRM Producers
 general
 COMAR database: http://www.bam.de
 individual suppliers
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IRMM:
BAM:
LGC:
NIST:
others...
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
http://www.irmm.jrc.be
http://www.bam.de
http://www.lgc.co.uk
http://www.nist.gov
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
General Statement
I use a CRM, therefore my
measurement result is
automatically correct
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching
Things to Remember
 very important component
 production is not trivial
 selection and use is not easy
 CRMs do not automatically
ensure quality outcome
Papadakis, I.: (Certified) Reference Materials
In: Wenclawiak, Koch, Hadjicostas (eds.)
© Springer-Verlag Berlin Heidelberg 2003
Quality Assurance in Analytical Chemistry – Training and Teaching