48

TERMINOLOGY AND DEFINITIONS

Accred Qual Assur (2001) 6 : 4850
Q Springer-Verlag 2001

Rainer Schmidt

Chemical aspects of
metrology in the chemical
industry
Abstract A brief description is given
about the role of metrology in the chemical industry both in production and analysis. Chemical aspects in metrology such
as sample stability, homogeneity, crosscontamination, cross-interference not
known to other measuring fields have to
be taken into account. The measurement
carried out to decide about the quality of
a chemical product must be fit for purpose. The measurement index (MI) can
be used as a readily available key figure
for this task. The quotient of the standard
deviation of the measurement and the
overall standard deviation of the process
defines the ability of a given method to
monitor process changes for a specific
test item. The definition, origin and quality of reference and working calibration
substances used are explained. Comparability to the first lab sample and consideration of the customers needs are of utmost importance in the chemical industry
whereas traceability to SI units is normally restricted to the calibration of laboratory equipment.

Metrology in chemical analysis covers

sampling, sample preparation and the
measurement itself. Chemical aspects include, e.g. sample stability, homogeneity,
cross-contamination and cross-interference. All of these contribute to the measurement uncertainty.

Measurement index (MI)

How precise must a measurement be in
the chemical industry to be fit for purpose? For in-process and final quality
control the total standard deviation consists of two major contributions: the
standard deviation of the process and the
standard deviation of the test method
(see Fig. 1).
The standard deviation of the process
cannot be evaluated directly. The standard deviation of the test method can be
determined, e.g. by analysing a calibration substance parallel to the process
sample or by evaluating/estimating the
measurement uncertainty. The quotient
of the total standard deviation and the
standard deviation of the test method can
be defined as the MI [2, 3].
MI p

Stotal
Stest method

where
S 2totalpS 2test methodcS 2process

The MI describes the capability of a

test method (including sampling) to monitor process changes. The relationship between MI and the quotient of the standard deviation and the variance is given in
Table 1.
For MI 1 3 the contribution of the test
method to the total variance is less than
11%. If necessary, the total standard deviation can only be decreased by improving the process (see Fig. 2). Improvement
of the analytical method would be a
waste of time and money.
For MI~2 the test method is not suitable to monitor any process changes but
it still might be capable of detecting out
of specification situations as shown in
Fig. 3.
In the car industry the quality assurance program QS 9000 requires an MI of
3.3 thus allowing a contribution of the
test method to the total variance of less
than 10% only [4].

Calibration substances
Reliable and reproducible results are obtained in analytical laboratories of the
chemical industry by using validated
methods, calibration substances, intraand interlaboratory comparisons and calibrated measurement equipment. Two
kinds of calibration substances are commonly used in the chemical industry.
A) Reference calibration substances: calibration substance having the highest
quality in a chemical company, from
which measurements made there are
derived.

Keywords Measurement index 7

Measurement uncertainty 7 Analytical
measurements 7 Traceability 7
Comparability

Introduction
Metrology is defined as the science of
measurement [1] and therefore covers
all measurements performed in the chemical industry.
Of course, all basic and a lot of derived SI units play an important role in
industrial chemistry. Temperature and
pressure have to be well controlled during chemical reactions, chemical products
are sold by weight and delivery has to be
just in time. The volume of the glassware
used in chemical analysis is well characterised, balances are calibrated with certified weights and traceable calibration
standards are readily available, e.g. for
pH-measurement.

Fig. 1 Quality control for a test item

Table 1 Correlation between the measurement index (MI) and the %-contribution of
the total standard deviation and the variance
MI
Stotal/
Stest method

Stest method/
Stotal*100[%]

S 2test method/
S 2total*100[%]

Suitability of the test method to monitor process changes

~2
23
13

1 13
1316
~ 6

1 25
2511
~11

No
Limited
Yes

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control these treasures and to keep them

at the highest quality assurance level possible.

Consideration of the customers

needs

Fig. 2 Sulphur in oil (quality control of a raw material)

Fig. 3 Content of an active substance in a rubber product (quality control of the final
product)

Origin: lab sample, one batch produced, commercially available product, specially synthesized product.
Qualitative calibration substance
(identified by MS and/or FTIR): used
for peak identification in chromatography only.
Quantitative calibration substance:
characterised by NMR, CHN and/or
elemental analysis, chromatographic,
gravimetric and/or titrimetric methods. The balance as a cross check
should be near to 100%.
B) Working calibration substances: calibration substance, used routinely to
calibrate or check measuring instruments in a chemical company, from
which measurements made there are
derived.
Qualitative calibration substance:
1. Genuine production sample
2. Spiked production sample
Quantitative calibration substance:
1. Pure substance calibrated against
the reference calibration substance
2. Synthetic sample
In a chromatogram of a fine chemical
product, peaks of interest normally include:

Raw material
Final product
Minor components
Unknowns (reported as sum and number).
Minor components are stated in the analytical test report, e.g. because
1) They cannot be separated in the final
cleaning step
2) Of their reactivity in the following
reaction
3) Of their poisonous effect on a catalyst
4) Of their toxic effects in a direct application.
The number of calibration substances
present in an analytical research department of a chemical company (fine chemicals) amounts to about 10,000. Every
year, 200400 new calibration substances
are added. The number of calibration
substances present in an routine analytical department of a chemical company
(fine chemicals) amounts to about 1000.
Every year, 4060 new calibration substances are added. Some of these substances are more expensive than gold,
some of them are only available in small
quantities. A lot of effort is invested in
the chemical industry to maintain and

A chemical product is not only characterised by weight but also by its purity and/
or by its chemical composition and/or by
its applicational properties. All of these
are important for the product to be fit for
purpose and all of these are linked to the
chemical reaction used to manufacture
the product. With respect to applicational
properties in following reaction steps,
even minor components can be of utmost
importance. Cleaning up does not always
improve a chemical product. Therefore
reproducible product quality within defined limits is needed. This cannot only
be achieved by analysing the final product. This also has to be integrated into
the manufacturing process. In many cases
changing the process or even the starting
material results in re-qualifying the final
product. This is definitely true for fine
chemicals but applies as well to bulk
products. Therefore Metrology in the
Chemical Industry understood as Consideration of the customers needs describes a procedure which insures the
product to be delivered is fit for purpose.
The intention is by no means to imply
obtaining results traceable to national or
international reference standards for the
test items analysed.
The procedure starts with the identification of the raw materials, e.g. by a
spectroscopic method, includes the reaction steps controlled by a check-list and
analytical in-process control tests, and finally ends with analysis of the product
sold. In this whole chain, measurement
uncertainty is normally only a minor contribution to the overall uncertainty of the
process. The main emphasis of the analyst is to obtain reliable and reproducible
results, i.e. comparability is more important than traceability.
The procedure described above is normally embedded in a quality management
system according to ISO 9001 and/or
EN 45001 and/or good manufacture practice (GMP). If a product is manufactured
without any deviation during reaction,
product handling and testing, there is a
great amount of confidence that the final
product will meet the fitness-for-purpose
criteria of the customer. A higher degree
of accuracy of the analytical method used
will not necessarily increase the level of
confidence but will contribute considerably to the costs of the overall process.
The customers needs are normally defined in the product specification in

50

which the limits and analytical methods

used are stated. If a lab sample is exchanged and the customer explicitly orders according to this sample, even unspecified items will be legally binding.
Therefore great care must be taken in a
later scale-up of the manufacturing process not to change any process parameters
which influence the defined product quality.

Conclusions
Metrology plays an important role in
the chemical industry.
Measurement traceability to values of
SI units is fulfilled, e.g. for analytical
equipment (temperature control, balance, etc.).
Consideration of the customers needs
is fulfilled by mutual agreement on a
product specification or a reference
(e.g. lab sample).
Comparability is achieved by using: validated methods, references, intra- and
interlaboratory comparisons, calibrated
measurement equipment.

The fitness-for-purpose criteria are expressed in the MI

Chemical aspects of the measurement
such as stability, cross-contamination,
reactivity, homogeneity, sampling, etc.
have to be taken into account
In the chemical industry complaints
about the quality of a product or the
quality of a measurement are rare compared to the number of orders performed
every day. Therefore the common goal in
the chemical industry is to maintain the
reached standard and to increase the customers confidence in the constancy of
the final product delivered.

References
1. ISO-VIM (1993) International vocabulary of basic and general terms in metrology, 2nd edn. International Organization for Standardization (ISO), Geneva, Switzerland; ISBN-92-67-01075-1
2. Brown A, Fleming J (1996) VAM Bulletin, Spring 1996. Laboratory of the
Government Chemist (LGC), Teddington, UK

3. Persijn M, van Nuland Y (1996) Qual

Eng 9 : 9598
4. Measurement Systems Analysis (MSA)
Requirements of the QS 9000,
Chrysler, Ford/Jaguar, Opel/Vauxhall
Carwin Continuous Ltd. Unit 1
Trade Link, Western Ave, West Thurrock, Grays, Essex, UK

Received: 25 April 2000

Accepted: 2 August 2000
Presented at Analytica Conference 2000,
1114 April 2000, Munich, Germany
R.A. Schmidt
Bayer AG, Chemicals Business Group,
Build. P1, 51368 Leverkusen, Germany
e-mail: Rainer.Schmidt.RS6bayer-ag.de
Tel.: c49-214-3028674
Fax: c49-214-3066391