- Email: [email protected]
QUALITY ASSURANCE | Traceability
QUALITY ASSURANCE / Traceability 477 Table 3 Contrast coefficients for a Plackett–Burman experimental design for seven influence factors Experiment
Factor
of the added material is known as the surrogate or marginal recovery. As with bias, recovery should be tested for significance and the result corrected if necessary.
1
2
3
4
5
6
7
þ – þ – – þ þ –
þ þ – þ – – þ –
þ þ þ – þ – – –
– þ þ þ – þ – –
– – þ þ þ – þ –
þ – – þ þ þ – –
– þ – – þ þ þ –
See also: Quality Assurance: Quality Control; Interlaboratory Studies; Reference Materials; Production of Reference Materials; Accreditation.
The sign of the contrast coefficient indicates the level of the factor: –, normal experimental level; þ , changed level. The effect of a factor is obtained by summing each experimental response multiplied by the contrast coefficient divided by 4 (number of experiments/2).
Burgess C (2000) Valid Analytical Methods and Procedures: A Best Practice Approach to Method Selection, Development and Evaluation. Cambridge: Royal Society of Chemistry. Christensen JM, Kristiansen J, Hansen AaM, and Nielsen JL (1995) Method validation: An essential tool in total quality management. In: Parkany M (ed.) Quality Assurance and TQM for Analytical Laboratories, pp. 46–54. Cambridge: Royal Society of Chemistry. Eurachem Working Group (1998) Eurachem Guide: The Fitness for Purpose of Analytical Methods. Teddington: LGC (Teddington) Ltd. Fajgelj A and Ambrus A (eds.) (2000) Principles and Practices of Method Validation. Cambridge: Royal Society of Chemistry. Green JM (1996) A practical guide to analytical method validation. Analytical Chemistry 68(9): 305A–309A. ICH (1995) ICH Q2A Text on Validation of Analytical Procedures. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Geneva, Switzerland. ICH (1996) ICH Q2B Validation of Analytical Procedures: Methodology. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Geneva, Switzerland. Thompson M, Ellison S, and Wood R (2002) Harmonized guidelines for single laboratory validation of methods of analysis. Pure and Applied Chemistry 74: 835–855. United States Pharmacopeial Convention (1999) The United States Pharmacopeia 24 – National Formulary 19, General Information, /1225S Validation of Compendial Methods, United States Pharmacopeial Convention, Inc., Rockville, Maryland.
1 2 3 4 5 6 7 8
Conventionally, the level labeled minus is the method value and the level labeled plus is the changed value. The calculation gives the average change in measurement result (which may be expressed as the change in the indication of the measuring system) when the parameter of interest changes from the method value to the changed value. The specification of the method validation has to decide what an acceptable effect is for each factor studied. Recovery
Recovery is a bias usually associated with sample preparation or pretreatment. It is expressed as the measurement result as a percentage of the certified value. To obtain a proper estimate of recovery a matrix CRM should be analyzed. This value is sometimes known as the analytical yield, or apparent recovery, to distinguish it from the recovery of spiked samples described below. If only pure analyte is available the surrogate recovery is obtained by analysis of a test material and then analyzed again after spiking with a known mass of pure analyte. The difference between the measurement results before and after spiking as a percentage
Further Reading
Traceability M Sargent, LGC Limited, Teddington, UK
Introduction
& 2005, Elsevier Ltd. All Rights Reserved.
Traceability is one of the principal requirements for achieving comparability of measurements across
478 QUALITY ASSURANCE / Traceability
different places and different periods of time. If measurements are to be accepted everywhere, they must not only be reliable but also be made on a comparable basis to those obtained elsewhere or at other times. Hence, international quality standards such as ISO 17025 stress the need for traceability to appropriate measurement references, as well as the more familiar requirements of operating in accordance with a comprehensive quality system and using properly validated methods. Whilst it may be feasible for two results to be compared directly when necessary, a more general approach is needed to provide comparability between many results obtained at different times or places. This can be achieved by linking each measurement result to a common reference point or measurement standard. Results may then be compared through their relationship to that common reference. The concept of linking results to a stable common reference point is termed traceability. Traceability is formally defined as the property of the result of a measurement or the value of a standard whereby it can be related to stated references, usually national or international standards, through an unbroken chain of comparisons all having stated uncertainties. This definition has achieved global acceptance in the metrology community, which is responsible for physical measurements such as time, mass, or length, and metrologists have worked for well over 100 years to achieve international comparability of their measurements in this way. The outcome has been an International Measurement System that is embraced by virtually every developed country in the world. This system is described in more detail later in this article. It is timely, however, to emphasize one aspect of traceability that is often misunderstood. Traceability is not an inherent property of the internationally recognized system of measurement units (the Syste`me International d’Unite´s, SI), such as the kilogram, meter, or mole. The concept of traceability works because a complex infrastructure has been developed within the International Measurement System to underpin the realization of these units. This infrastructure allows measurement institutes around the world to regularly intercompare their measurement standards or procedures. This provides a global basis for the reference points that these institutes use for the measurement services they provide to industry and other users. These services include traceable standards or calibration facilities that are available to end users, either directly or through secondary suppliers. The International Measurement System also provides a framework within which these institutes can
collaborate to resolve measurement differences and improve measurement techniques. The International Measurement System underpins accurate and comparable measurements by ensuring that each measurement result for a particular parameter is traceable to a reference that is accepted throughout the world. The original point of reference for each unit was a unique artifact kept at a laboratory near Paris (see below), for example, the international standard meter or kilogram. More recently, the emphasis has been on realization of the relevant base (SI) unit as a standard of measurement, usually achieved through development of an extremely accurate measurement procedure for that parameter. In either case, the concept of traceability depends on a chain of measurements linked back to the appropriate international primary standard through a series of calibrations (i.e., comparisons between two standards in the chain). Provided that the uncertainties of the comparisons are known, a measurement result obtained through calibration against one of these standards will itself be traceable to the agreed reference.
Development of the International Measurement System The basis for international metrology was established in Paris in 1875 when a diplomatic treaty entitled the ‘Convention of the Metre’ was signed by representatives of 17 nations. That Convention, which was modified slightly in 1921, now has 51 Member States, including all the major industrialized countries. It remains the basis of all international agreement on units of measurement and, as mentioned above, embraces not only the traditional physical quantities but also areas such as radiation, chemistry, and biology. In order to achieve its aims, the Convention established a permanent organizational structure to enable member governments to work together on matters relating to units of measurement. The key components of this structure, which are shown in Figure 1, were the Confe´rence Ge´ne´rale des Poids et Mesures (CGPM), the Comite´ International des Poids et Mesures (CIPM), and the Bureau International des Poids et Mesures (BIPM). Since 1875, the need to demonstrate equivalence between national measurement standards has been met by the BIPM, which is located at Se´vres near Paris, working in collaboration with the national metrology institutes (NMIs) of the member states. The same organizations have also worked together to meet the need for measurement standards of ever increasing accuracy, range, and diversity. These
QUALITY ASSURANCE / Traceability 479
Associate States and Economies of the CGPM
Metre Convention 1875
Diplomatic treaty
General Conference on Weights and Measures (CGPM) meets every four years and consists of delegates from Member States
Governments of Member States
International Committee for Weights and Measures (CIPM) consists of eighteen individuals elected by the CGPM It is charged with supervision of the BIPM and affairs of the Metre Convention
International organizations
The CIPM meets annually at the BIPM
CIPM MRA
Consulative Committees (CCs) Ten CCs normally chaired by a member of CIPM; to advise the CIPM; act on technical matters and take important role in CIPM MRA; comprise representatives of NMIs and other experts
National metrology institutes (NMIs)
International Bureau of Weights and Measures (BIPM) International center for metrology Laboratories and offices at Sévres Figure 1 The structure of the international measurement system established by the Convention of the Metre in 1875. The chart shows the key international organizations and the links between them. (Reproduced with permission from the BIPM website.)
collaborative technical activities are achieved primarily through a number of Consultative Committees, each of which addresses a specific area of measurement and is normally chaired by a member of the CIPM. A major step forward in the development of international metrology took place at a meeting held in Paris on October 14, 1999, with the establishment of a Mutual Recognition Arrangement (MRA) for national measurement standards and for calibration and measurement certificates issued by NMIs. The MRA was initially signed by the NMIs of 38 Member States and representatives of two international organizations. This Arrangement is a response to a growing need for a comprehensive scheme to give users reliable quantitative information on the
comparability of national metrology services and to provide the technical basis for wider agreements negotiated for international trade, commerce, and regulatory affairs. The organization and participation in the MRA is summarized in Figure 2. A key feature of the MRA is the development of a BIPM key comparison database (KCDB), which includes the results of key and supplementary comparisons (KCs) and the calibration and measurement capabilities (CMCs) of the NMI signatories to the MRA. Key comparisons are high-level interlaboratory comparisons of the standards or measurement procedures of the participating institutes. The scheme for organizing such comparisons is shown in Figure 3. The comparisons are operated in the same way as proficiency testing (PT) schemes, i.e.,
480 QUALITY ASSURANCE / Traceability Mutual Recognition Arrangement National Metrology Institutes National measurement standards
Key comparisons
Consultative Committees RMOs BIPM
y ke . O upp RM+ s
JCRB (Joint Committee of the RMOs and the BIPM) Calibration measurement capabilities
In
fo
rm
at
ion
Degrees of equivalence
Supplementary comparisons to support calibrations
Submissions
Info rma t
Consultative Committees
Quality systems
Regional Metrology Organizations (RMOs)
ion
Results
Calibration measurement capabilities
MRA appendix B
MRA appendix C
Key comparison database BIPM Figure 2 The organization of the BIPM Mutual Recognition Arrangement (MRA), agreed in 1999 between the directors of the national measurement institutes of 38 Member States and representatives of two international organizations. (Reproduced with permission from BIPM website.)
Scheme for key comparisons
RMO key comparisons
BIPM
RMO key comparisons
CIPM key comparisons
RMO key comparisons RMO key comparisons
BIPM NMI participating in CIPM key comparisons NMI participating in CIPM key comparisons and in RMO key comparisons NMI participating in RMO key comparisons NMI participating in ongoing BIPM key comparisons NMI participating in a bilateral key comparison
BIPM
International organization signatory to MRA Figure 3 The scheme of key comparisons established in order to support the aims of the Mutual Recognition Arrangement (MRA) and to derive the degree of equivalence between the standards or calibration services of participating national measurement institutes. (Reproduced with permission from BIPM website.)
QUALITY ASSURANCE / Traceability 481
standards or samples for intercomparison are circulated to laboratories and measured blind. Moreover, once an institute has agreed to participate in a KC it cannot withdraw its measurement results. The key comparison database is openly accessible through the BIPM website (http:/www.bipm.org). Once agreed by the participants and approved by the relevant consultative committee, the results of each key comparison are added to the database. The CMCs of the NMIs are also published in the key comparison database. These capabilities are submitted by each institute in accordance with the services that it offers. CMCs are subjected to two important safeguards to ensure that users of these services obtain traceable data of demonstrable equivalence with data provided by other member institutes. The safeguards are (1) the requirement that each institute should participate in relevant KCs, and demonstrate that its performance is commensurate with its claimed capabilities, and (2) a review procedure that involves experts from all MRA member institutes working at both the regional and global levels.
The Need for Traceability in Analytical Chemistry There are relatively few traceable chemical measurement standards in the sense used for physical measurement standards and the concept of traceable measurements is not widely understood by today’s analysts. Nevertheless, the need for comparability of measurement results is just as important in analytical chemistry as in physical metrology. Classical analytical chemistry did, indeed, depend on traceable calibration of balances and volumetric glassware to achieve comparable data between laboratories. Prior to the extensive use of instrumentation, analytical laboratory procedures placed emphasis on the origin of the calibrated weights and glassware used, for example, in gravimetric or titrimetric analysis methods and the need to safeguard the integrity of these artifacts. In many analytical laboratories at that time, only a single set of balance weights was externally calibrated and traceable to a national reference; calibration of other balance weights or volumetric glassware was achieved using the set of reference weights and was an important, routine aspect of laboratory operations. In order to understand traceability in chemistry, it is important to appreciate what underlies the use of calibrated weights in this way. It will also become apparent why the concept of traceability seemed less relevant to chemistry as analytical laboratories moved away
from classical analysis and adopted instrumental techniques. Regardless of the need for traceable calibration of balance weights and volumetric glassware, analytical chemistry is not concerned per se with the determination of mass and volume. Its purpose is to determine amount of substance, i.e., the amount of a specific chemical entity such as, for example, copper, potassium dichromate, or ethanol. This is reflected in the definition of the SI unit for chemistry, the mole (symbol: mol). The mole is the amount of substance of a system that contains as many elementary entities as there are atoms in 0.012 kilogram of carbon-12. When the mole is used, the elementary entities must be specified and may be atoms, molecules, ions, electrons, other particles, or specified groups of such particles. In some application areas such as, for example, the clinical sector, the mole is a widely used unit whereas in others, such as industrial or environmental analysis, it is more common to use units based on mass (e.g., milligram per kilogram) or parts per million (ppm). Nevertheless, it is important to remember that, regardless of the preferred unit, the chemist is measuring a chemical entity which must be correctly identified and for which a chemical standard is required. This is a fundamental requirement for traceability in chemistry. In the classical analytical laboratory, it was common practice for the chemist to prepare chemical standards in-house using a knowledge of chemistry to ensure that they comprised the correct substance and were of sufficient purity for the purpose in hand. Clearly, any error in assessing the identity or purity of such a chemical standard will affect the reliability of measurements dependent on it, just as will errors in weight and volume when using an aliquot of the chemical standard to prepare a calibration solution. This situation was reflected in the growth of the chemical reagent industry, supplying initially the chemical materials and more recently certified calibration solutions. In order to ensure reliable reagents, each supplier adhered to an agreed specification, which might be its own, one agreed within an area of trade, or an international standard. These specifications were, however, largely local or sectorbased; no attempt was made to adopt the concept of traceability to provide an international basis for all such materials or to implement a single, international infrastructure to underpin it. This situation existed partly due to a widespread perception, which continues to this day, that errors in the preparation of calibration standards are not the most pressing problem facing analytical chemists. This arises because calibration using chemical standards is complicated by the dependence of the
482 QUALITY ASSURANCE / Traceability
chemical measurement process on the sample matrix. In the classical laboratory this problem was overcome by quantitative removal of the analyte from the matrix prior to measurement or by using appropriate chemistry to overcome matrix interferences. In the modern laboratory the analysis is almost invariably instrument based but the instrumental determination is often the final step of a complex analytical method involving extensive pretreatment of the sample. Hence, calibration of the instrument using a pure chemical standard, even a traceable one, is on its own insufficient to achieve reliable and comparable results. The sample matrix problem has stimulated the development of two pragmatic solutions: matrix reference materials and interlaboratory comparisons. The matrix-matched, certified reference material (CRM) is a unique type of chemical standard commonly used to validate complete measurement methods and sometimes for instrumental calibration (e.g., in XRF). Such standards must be available for each required analyte/matrix combination. Similarly, interlaboratory comparisons are undertaken for each relevant analyte/matrix combination in order to establish comparability of data between laboratories. These comparisons range from round robin studies, which collaboratively test a new method, to formal PT schemes that assess agreement between laboratories on an ongoing basis. CRMs and PT schemes have been used by analysts with reasonable success over many years but they both have a number of technical, practical, and economic limitations. The need for a wide variety of application-specific CRMs has lead to fragmented production without any formal relationship between the certified values of CRMs produced for different applications or by different organizations. There are thousands of CRMs in use but many of those required for critical applications such as manufacturing, trade, health, or the environment are unavailable. In addition, production costs are high and it is difficult or impossible to manufacture sufficiently stable CRMs for some applications. Interlaboratory comparisons also have a number of limitations, particularly that they are time-consuming and expensive. Comparability usually extends only to the immediate participants in a single comparison because comparability between different comparisons is rarely established, even when they are coordinated by the same organization. It is impracticable to organize comparisons for every routine application or to organize a worldwide comparison involving all the laboratories requiring comparability for each measurement application. These problems have long been recognized as a significant technical and economic limitation in
delivering sound chemical analysis data. The situation is steadily worsening with increasing demand from purchasers of data and by regulators for proven comparability of measurements. This is for several reasons. Global expansion of trade, which means more countries and more laboratories need to be brought into each interlaboratory comparison. In addition, increasing numbers of measurements are used in support of regulations, for which there is an expanding requirement for rigorously proven reliability and comparability. Finally, increasing use of subcontracted measurements, due to commercial pressures on laboratories, requires not only conformity of contractors to quality systems but also demonstration of the comparability of data from different contractors. To ensure reliable and comparable chemical measurements in the twenty-first century, it is desirable to have in place a unified international system based on the traceability of measurement results.
Achieving Traceability in Analytical Chemistry Traceable chemical measurement results require a measurement infrastructure analogous to the systems that underpin physical measurements, as described above. Chemical measurements have developed more or less on a sectorial basis and in a different culture, so that the systems developed for physical measurements cannot easily be directly applied to chemical or, indeed, biological measurements. In most countries, expertise in chemical metrology is also more widely dispersed than is the case for physical measurements, which are mainly focused on a single national measurement institute. Traceable measurements also require that the uncertainty of the entire chemical measurement procedure is fully understood. The uncertainty of the sample preparation and pretreatment is, however, largely an empirical estimate and the uncertainty associated with taking the initial sample or subsample is often overlooked. Developing reference methods that offer improved and rigorously determined levels of uncertainty for difficult sample matrices is a key factor in solving this problem. In order to address both the technical and organizational problems, the CIPM (see Figure 1) decided in 1993 to establish an international, collaborative program of work in chemistry. This program is organized through the CIPM’s Comite´ Consultatif pour la Quantite´ de Matie`re (CCQM) – the committee for metrology in chemistry. The CCQM’s task is to resolve the practical difficulties of achieving comparable chemical measurements through traceability and to provide an international structure of
QUALITY ASSURANCE / Traceability 483
chemical laboratories. These laboratories are signatories to the BIPM MRA (see above) and are required to demonstrate the equivalence of their measurement data through measurement comparisons as well as implementing a quality management system for their calibration or measurement certificates. Once this has been done, claims may be submitted by each institute listing its measurement capabilities, i.e., standards or calibration services that it provides. These are vetted by peer review before inclusion in the BIPM Key Comparison Database. The CCQM has organized an ongoing series of key comparisons that reflect important applications relevant to industry, trade, health, and the environment, not just measurements on single-substance calibration standards. An example of some of the current CCQM entries in the BIPM database can be seen in Figure 4. The results for one such Key Comparison, CCQMK13, listed in Figure 4, are shown in Figure 5. This example illustrates a trace analysis application, the determination of lead in a sediment. The error bars
represent the expanded uncertainty reported by each participating national measurement institute. Bearing in mind that this is a difficult trace determination, these uncertainties and the degree of equivalence between the individual results (shown on the y-axis) illustrate how the participating institutes are working at the limits of current analytical methodology. This is necessary because, in order to underpin internationally traceable measurements, data from these laboratories form the ultimate reference points for calibration chains that end with routine measurements by field laboratories. Each calibration stage in such a chain introduces an increase in the uncertainty of the resulting measurement. Hence, unless the calibration chains can be kept very short, the national measurement institutes must achieve uncertainties substantially smaller than those needed by the field laboratories. As mentioned above, the BIPM Key Comparison Database provides access to the measurement capabilities of these institutes. Each such entry shows the dissemination range in terms of both the available concentration range and the
Key and supplementary comparisons Search criteria: amount of substance, inorganics your request produced 11 result(s) List of comparisons Click on a comparison identifier to view more CCQM-K2 Comparison type, Field Status CCQM-K8 Comparison type, Field Status CCQM-K13 Comparison type, Field Status CCQM-K14 Comparison type, Field Status CCQM-K24 Comparison type, Field Status
Page 1 2 3
Cadmium and lead in natural water 1998 Key comparison in amount of substance, inorganics Approved for equivalence, Results available Monoelemental calibration solutions of Al, Cu, Fe, and Mg 1999−2000 Key comparison in amount of substance, inorganics Approved for equivalence, Results available Amount content of cadmium (Cd) and lead (Pb) in sediment 2000 Key comparison in amount of substance, inorganics Approved for equivalence, Results available Calcium in human serum 2003 Key comparison in amount of substance, inorganics Measurements completed Cadmium (Cd) in rice 2001 Key comparison in amount of substance, inorganics Approved for equivalence, Results available
Figure 4 Part of a table taken from the BIPM Key Comparison Database (KCDB) which may be viewed on the BIPM website (www.bipm.org). The table shows some of the chemistry key comparisons organized by the working groups of the CCQM. (Reproduced with permission from BIPM website.)
484 QUALITY ASSURANCE / Traceability CCQM–K13: Lead in sediment, amount content ~170 µmol kg –1
Degrees of equivalence (µmol kg –1)
10
5
0
–5
–10 Uncertainty bars shows with coverage factor of 2 VNIIM
PTB
NRCCRM
NRC
NIST
NIMC
NARL
BNM–LNE
LGC
KRISS
IRMM
CSIR–NML
CENAM
BAM
–15
Figure 5 Results of one of the key comparisons listed in the BIPM Key Comparison Database, CCQM-K13, which concerns the determination of lead in sediment samples at trace levels. This information may be viewed on the BIPM website (www.bipm.org). (Reproduced with permission from BIPM website.)
Calibration and measurement capabilities Sediments, soils, ores, and particulates United Kingdom, LGC (Laboratory of the Government Chemist) Complete CMCs in Amount of substance for sediments, soils, ores, and particulates for United Kingdom (.pdf file) Dissemination range of measurement capability Analyte or Matrix or Mass fraction in Relative expanded uncertainty in component material µg per g % Lead 30–90 2–3 Sediment Figure 6 An example of a measurement capability (CMC) submitted for international peer review and accepted for inclusion in the BIPM Key Comparison Database. This example shows a relevant CMC for one of the institutes that participated in CCQM-K13 (illustrated in Figure 5). The database presently comprises several thousand CMCs, including a wide range of chemical measurements. (Reproduced with permission from BIPM website.)
corresponding range of measurement uncertainty. A typical CMC entry from one institute, for the capability tested by CCQM-K13, is shown in Figure 6.
Traceability and Measurement Uncertainty It should be clear from the above discussion that, regardless of the availability of standards, reference materials or calibration services having reference values exhibiting international traceability, the results dependent on them will not be traceable unless field laboratories are able to obtain reliable estimates of their own measurement uncertainty. This is, in fact, a requirement for accreditation to ISO 17025 but the practical difficulties of achieving it for
chemical measurements are considerable. It is well known that the uncertainties of analytical results are often large because many analytical methods require several quite complex operations (e.g., extraction, clean-up, or preconcentration) prior to the final measurement using a calibrated instrument. The uncertainty associated with these stages is frequently difficult, or sometimes impossible, to quantify and the analyst must resort to an estimate based on the available data and previous experience. Nevertheless, it is essential that laboratories strive to achieve the best possible estimate of uncertainty at the method validation stage. A key factor in this regard is the availability of appropriate matrix reference materials. In order to achieve routine results that are both reliable and traceable, it is essential that
QUALITY ASSURANCE / Accreditation 485
validation is based on materials that are both similar to the routine samples and have reference values with substantially smaller uncertainties than is required for routine data. Of equal importance is developing a base of knowledge and expertise that can help laboratories to resolve some of the problems encountered in evaluating the uncertainties of analytical results. Achieving these goals will not happen overnight but adopting the twin principles of measurement traceability and uncertainty offers analytical scientists a route map by which they may be achieved.
Acknowledgments The diagrams illustrating the international measurement system and the examples from the BIPM Key Comparison Database were provided by the Bureau International des Poids et Mesures, Se´vres, France, and are reproduced with their permission. See also: Quality Assurance: Reference Materials; Method Validation.
Further Reading EN-ISO/IEC 17025:2000 (2000) Requirements for the Competence of Testing and Calibration Laboratories. Geneva: International Standards Organisation. EURACHEM (1998) The Fitness for Purpose of Analytical Methods: A Laboratory Guide to Method Validation and
Related Topics. Available from the EURACHEM website (http://www.eurachem.ul.pt). EURACHEM (2000) Quantifying Uncertainty in Analytical Measurements, 2nd edn. Available from the EURACHEM website (http://www.eurachem.ul.pt). EURACHEM (2002) The Selection and Use of Reference Materials; A Basic Guide for Laboratories and Accreditation Bodies, EEE/RM/062. Available from the EURACHEM website (http://www.eurachem.ul.pt). EURACHEM/CITAC (2002) Guide to Quality in Analytical Chemistry. Available from the EURACHEM (http:// www.eurachem.ul.pt) or CITAC (http://www.citac.cc) websites. EURACHEM/CITAC (2003) Traceability in Chemical Measurement, A Guide to Achieving Comparable Results in Chemical Measurement. Available from the Eurachem website (http://www.eurachem.ul.pt). International Organization for Standardization (ISO) (1995) Guide to the Expression of Uncertainty in Measurement. Geneva: ISO. ISO (1993) International Vocabulary of Basic and General Terms in Metrology. Geneva: International Standards Organization. McNaught AD and Wilkinson A (1997) IUPAC Compendium of Chemical Terminology, 2nd edn. Cambridge, UK: Royal Society of Chemistry. Stoeppler M, Wolf WR, and Jenks PJ (2000) Reference Materials for Chemical Analysis. New York: Wiley-Interscience. Taylor JK (1993) Handbook for SRM Users, NBS Special Publication 260-100. Gaithersburg: National Institute of Standards and Technology.
Accreditation E J Newman, Newman, Bucknell Associates, Wimborne, UK & 2005, Elsevier Ltd. All Rights Reserved.
Introduction One indication of the importance of analytical chemistry is that it has been estimated that B3% of the gross domestic product of the more advanced industrial nations is spent on analytical testing. Other indications of importance come from major areas of application of analytical science, such as: food safety, drinking water quality, animal feeds, fertilizers and pesticides; air and coastal water quality monitoring, workplace health and safety monitoring, and applications to the environment generally. Also applications in the field of health care including the quality control (QC) of pharmaceuticals, and clinical analyses for both diagnosis and to monitor the effects of
therapy; the wide area of forensic science in which analytical chemistry is a core subject; and the many and varied important industries not included in the above, in which analysis provides vital QC, and which range from the long-established, such as steelmaking or dyeing, to the modern manufactures of microprocessors, optical fibers, and other advanced materials. To meet all these and many other demands, analysts produce, as a conservative estimate, over a billion items of analytical data every year in the United Kingdom alone. It is clear from this that analytical data provide the basis for thousands of important, even critical, decisions every day of the year. Furthermore, the importance of chemical analysis is increasing as legislators, considering scientific evidence, much of which was itself derived from analytical chemistry, continue to frame regulatory requirements, which can be enforced only by the endeavors of skilled analysts.
Factor
of the added material is known as the surrogate or marginal recovery. As with bias, recovery should be tested for significance and the result corrected if necessary.
1
2
3
4
5
6
7
þ – þ – – þ þ –
þ þ – þ – – þ –
þ þ þ – þ – – –
– þ þ þ – þ – –
– – þ þ þ – þ –
þ – – þ þ þ – –
– þ – – þ þ þ –
See also: Quality Assurance: Quality Control; Interlaboratory Studies; Reference Materials; Production of Reference Materials; Accreditation.
The sign of the contrast coefficient indicates the level of the factor: –, normal experimental level; þ , changed level. The effect of a factor is obtained by summing each experimental response multiplied by the contrast coefficient divided by 4 (number of experiments/2).
Burgess C (2000) Valid Analytical Methods and Procedures: A Best Practice Approach to Method Selection, Development and Evaluation. Cambridge: Royal Society of Chemistry. Christensen JM, Kristiansen J, Hansen AaM, and Nielsen JL (1995) Method validation: An essential tool in total quality management. In: Parkany M (ed.) Quality Assurance and TQM for Analytical Laboratories, pp. 46–54. Cambridge: Royal Society of Chemistry. Eurachem Working Group (1998) Eurachem Guide: The Fitness for Purpose of Analytical Methods. Teddington: LGC (Teddington) Ltd. Fajgelj A and Ambrus A (eds.) (2000) Principles and Practices of Method Validation. Cambridge: Royal Society of Chemistry. Green JM (1996) A practical guide to analytical method validation. Analytical Chemistry 68(9): 305A–309A. ICH (1995) ICH Q2A Text on Validation of Analytical Procedures. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Geneva, Switzerland. ICH (1996) ICH Q2B Validation of Analytical Procedures: Methodology. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Geneva, Switzerland. Thompson M, Ellison S, and Wood R (2002) Harmonized guidelines for single laboratory validation of methods of analysis. Pure and Applied Chemistry 74: 835–855. United States Pharmacopeial Convention (1999) The United States Pharmacopeia 24 – National Formulary 19, General Information, /1225S Validation of Compendial Methods, United States Pharmacopeial Convention, Inc., Rockville, Maryland.
1 2 3 4 5 6 7 8
Conventionally, the level labeled minus is the method value and the level labeled plus is the changed value. The calculation gives the average change in measurement result (which may be expressed as the change in the indication of the measuring system) when the parameter of interest changes from the method value to the changed value. The specification of the method validation has to decide what an acceptable effect is for each factor studied. Recovery
Recovery is a bias usually associated with sample preparation or pretreatment. It is expressed as the measurement result as a percentage of the certified value. To obtain a proper estimate of recovery a matrix CRM should be analyzed. This value is sometimes known as the analytical yield, or apparent recovery, to distinguish it from the recovery of spiked samples described below. If only pure analyte is available the surrogate recovery is obtained by analysis of a test material and then analyzed again after spiking with a known mass of pure analyte. The difference between the measurement results before and after spiking as a percentage
Further Reading
Traceability M Sargent, LGC Limited, Teddington, UK
Introduction
& 2005, Elsevier Ltd. All Rights Reserved.
Traceability is one of the principal requirements for achieving comparability of measurements across
478 QUALITY ASSURANCE / Traceability
different places and different periods of time. If measurements are to be accepted everywhere, they must not only be reliable but also be made on a comparable basis to those obtained elsewhere or at other times. Hence, international quality standards such as ISO 17025 stress the need for traceability to appropriate measurement references, as well as the more familiar requirements of operating in accordance with a comprehensive quality system and using properly validated methods. Whilst it may be feasible for two results to be compared directly when necessary, a more general approach is needed to provide comparability between many results obtained at different times or places. This can be achieved by linking each measurement result to a common reference point or measurement standard. Results may then be compared through their relationship to that common reference. The concept of linking results to a stable common reference point is termed traceability. Traceability is formally defined as the property of the result of a measurement or the value of a standard whereby it can be related to stated references, usually national or international standards, through an unbroken chain of comparisons all having stated uncertainties. This definition has achieved global acceptance in the metrology community, which is responsible for physical measurements such as time, mass, or length, and metrologists have worked for well over 100 years to achieve international comparability of their measurements in this way. The outcome has been an International Measurement System that is embraced by virtually every developed country in the world. This system is described in more detail later in this article. It is timely, however, to emphasize one aspect of traceability that is often misunderstood. Traceability is not an inherent property of the internationally recognized system of measurement units (the Syste`me International d’Unite´s, SI), such as the kilogram, meter, or mole. The concept of traceability works because a complex infrastructure has been developed within the International Measurement System to underpin the realization of these units. This infrastructure allows measurement institutes around the world to regularly intercompare their measurement standards or procedures. This provides a global basis for the reference points that these institutes use for the measurement services they provide to industry and other users. These services include traceable standards or calibration facilities that are available to end users, either directly or through secondary suppliers. The International Measurement System also provides a framework within which these institutes can
collaborate to resolve measurement differences and improve measurement techniques. The International Measurement System underpins accurate and comparable measurements by ensuring that each measurement result for a particular parameter is traceable to a reference that is accepted throughout the world. The original point of reference for each unit was a unique artifact kept at a laboratory near Paris (see below), for example, the international standard meter or kilogram. More recently, the emphasis has been on realization of the relevant base (SI) unit as a standard of measurement, usually achieved through development of an extremely accurate measurement procedure for that parameter. In either case, the concept of traceability depends on a chain of measurements linked back to the appropriate international primary standard through a series of calibrations (i.e., comparisons between two standards in the chain). Provided that the uncertainties of the comparisons are known, a measurement result obtained through calibration against one of these standards will itself be traceable to the agreed reference.
Development of the International Measurement System The basis for international metrology was established in Paris in 1875 when a diplomatic treaty entitled the ‘Convention of the Metre’ was signed by representatives of 17 nations. That Convention, which was modified slightly in 1921, now has 51 Member States, including all the major industrialized countries. It remains the basis of all international agreement on units of measurement and, as mentioned above, embraces not only the traditional physical quantities but also areas such as radiation, chemistry, and biology. In order to achieve its aims, the Convention established a permanent organizational structure to enable member governments to work together on matters relating to units of measurement. The key components of this structure, which are shown in Figure 1, were the Confe´rence Ge´ne´rale des Poids et Mesures (CGPM), the Comite´ International des Poids et Mesures (CIPM), and the Bureau International des Poids et Mesures (BIPM). Since 1875, the need to demonstrate equivalence between national measurement standards has been met by the BIPM, which is located at Se´vres near Paris, working in collaboration with the national metrology institutes (NMIs) of the member states. The same organizations have also worked together to meet the need for measurement standards of ever increasing accuracy, range, and diversity. These
QUALITY ASSURANCE / Traceability 479
Associate States and Economies of the CGPM
Metre Convention 1875
Diplomatic treaty
General Conference on Weights and Measures (CGPM) meets every four years and consists of delegates from Member States
Governments of Member States
International Committee for Weights and Measures (CIPM) consists of eighteen individuals elected by the CGPM It is charged with supervision of the BIPM and affairs of the Metre Convention
International organizations
The CIPM meets annually at the BIPM
CIPM MRA
Consulative Committees (CCs) Ten CCs normally chaired by a member of CIPM; to advise the CIPM; act on technical matters and take important role in CIPM MRA; comprise representatives of NMIs and other experts
National metrology institutes (NMIs)
International Bureau of Weights and Measures (BIPM) International center for metrology Laboratories and offices at Sévres Figure 1 The structure of the international measurement system established by the Convention of the Metre in 1875. The chart shows the key international organizations and the links between them. (Reproduced with permission from the BIPM website.)
collaborative technical activities are achieved primarily through a number of Consultative Committees, each of which addresses a specific area of measurement and is normally chaired by a member of the CIPM. A major step forward in the development of international metrology took place at a meeting held in Paris on October 14, 1999, with the establishment of a Mutual Recognition Arrangement (MRA) for national measurement standards and for calibration and measurement certificates issued by NMIs. The MRA was initially signed by the NMIs of 38 Member States and representatives of two international organizations. This Arrangement is a response to a growing need for a comprehensive scheme to give users reliable quantitative information on the
comparability of national metrology services and to provide the technical basis for wider agreements negotiated for international trade, commerce, and regulatory affairs. The organization and participation in the MRA is summarized in Figure 2. A key feature of the MRA is the development of a BIPM key comparison database (KCDB), which includes the results of key and supplementary comparisons (KCs) and the calibration and measurement capabilities (CMCs) of the NMI signatories to the MRA. Key comparisons are high-level interlaboratory comparisons of the standards or measurement procedures of the participating institutes. The scheme for organizing such comparisons is shown in Figure 3. The comparisons are operated in the same way as proficiency testing (PT) schemes, i.e.,
480 QUALITY ASSURANCE / Traceability Mutual Recognition Arrangement National Metrology Institutes National measurement standards
Key comparisons
Consultative Committees RMOs BIPM
y ke . O upp RM+ s
JCRB (Joint Committee of the RMOs and the BIPM) Calibration measurement capabilities
In
fo
rm
at
ion
Degrees of equivalence
Supplementary comparisons to support calibrations
Submissions
Info rma t
Consultative Committees
Quality systems
Regional Metrology Organizations (RMOs)
ion
Results
Calibration measurement capabilities
MRA appendix B
MRA appendix C
Key comparison database BIPM Figure 2 The organization of the BIPM Mutual Recognition Arrangement (MRA), agreed in 1999 between the directors of the national measurement institutes of 38 Member States and representatives of two international organizations. (Reproduced with permission from BIPM website.)
Scheme for key comparisons
RMO key comparisons
BIPM
RMO key comparisons
CIPM key comparisons
RMO key comparisons RMO key comparisons
BIPM NMI participating in CIPM key comparisons NMI participating in CIPM key comparisons and in RMO key comparisons NMI participating in RMO key comparisons NMI participating in ongoing BIPM key comparisons NMI participating in a bilateral key comparison
BIPM
International organization signatory to MRA Figure 3 The scheme of key comparisons established in order to support the aims of the Mutual Recognition Arrangement (MRA) and to derive the degree of equivalence between the standards or calibration services of participating national measurement institutes. (Reproduced with permission from BIPM website.)
QUALITY ASSURANCE / Traceability 481
standards or samples for intercomparison are circulated to laboratories and measured blind. Moreover, once an institute has agreed to participate in a KC it cannot withdraw its measurement results. The key comparison database is openly accessible through the BIPM website (http:/www.bipm.org). Once agreed by the participants and approved by the relevant consultative committee, the results of each key comparison are added to the database. The CMCs of the NMIs are also published in the key comparison database. These capabilities are submitted by each institute in accordance with the services that it offers. CMCs are subjected to two important safeguards to ensure that users of these services obtain traceable data of demonstrable equivalence with data provided by other member institutes. The safeguards are (1) the requirement that each institute should participate in relevant KCs, and demonstrate that its performance is commensurate with its claimed capabilities, and (2) a review procedure that involves experts from all MRA member institutes working at both the regional and global levels.
The Need for Traceability in Analytical Chemistry There are relatively few traceable chemical measurement standards in the sense used for physical measurement standards and the concept of traceable measurements is not widely understood by today’s analysts. Nevertheless, the need for comparability of measurement results is just as important in analytical chemistry as in physical metrology. Classical analytical chemistry did, indeed, depend on traceable calibration of balances and volumetric glassware to achieve comparable data between laboratories. Prior to the extensive use of instrumentation, analytical laboratory procedures placed emphasis on the origin of the calibrated weights and glassware used, for example, in gravimetric or titrimetric analysis methods and the need to safeguard the integrity of these artifacts. In many analytical laboratories at that time, only a single set of balance weights was externally calibrated and traceable to a national reference; calibration of other balance weights or volumetric glassware was achieved using the set of reference weights and was an important, routine aspect of laboratory operations. In order to understand traceability in chemistry, it is important to appreciate what underlies the use of calibrated weights in this way. It will also become apparent why the concept of traceability seemed less relevant to chemistry as analytical laboratories moved away
from classical analysis and adopted instrumental techniques. Regardless of the need for traceable calibration of balance weights and volumetric glassware, analytical chemistry is not concerned per se with the determination of mass and volume. Its purpose is to determine amount of substance, i.e., the amount of a specific chemical entity such as, for example, copper, potassium dichromate, or ethanol. This is reflected in the definition of the SI unit for chemistry, the mole (symbol: mol). The mole is the amount of substance of a system that contains as many elementary entities as there are atoms in 0.012 kilogram of carbon-12. When the mole is used, the elementary entities must be specified and may be atoms, molecules, ions, electrons, other particles, or specified groups of such particles. In some application areas such as, for example, the clinical sector, the mole is a widely used unit whereas in others, such as industrial or environmental analysis, it is more common to use units based on mass (e.g., milligram per kilogram) or parts per million (ppm). Nevertheless, it is important to remember that, regardless of the preferred unit, the chemist is measuring a chemical entity which must be correctly identified and for which a chemical standard is required. This is a fundamental requirement for traceability in chemistry. In the classical analytical laboratory, it was common practice for the chemist to prepare chemical standards in-house using a knowledge of chemistry to ensure that they comprised the correct substance and were of sufficient purity for the purpose in hand. Clearly, any error in assessing the identity or purity of such a chemical standard will affect the reliability of measurements dependent on it, just as will errors in weight and volume when using an aliquot of the chemical standard to prepare a calibration solution. This situation was reflected in the growth of the chemical reagent industry, supplying initially the chemical materials and more recently certified calibration solutions. In order to ensure reliable reagents, each supplier adhered to an agreed specification, which might be its own, one agreed within an area of trade, or an international standard. These specifications were, however, largely local or sectorbased; no attempt was made to adopt the concept of traceability to provide an international basis for all such materials or to implement a single, international infrastructure to underpin it. This situation existed partly due to a widespread perception, which continues to this day, that errors in the preparation of calibration standards are not the most pressing problem facing analytical chemists. This arises because calibration using chemical standards is complicated by the dependence of the
482 QUALITY ASSURANCE / Traceability
chemical measurement process on the sample matrix. In the classical laboratory this problem was overcome by quantitative removal of the analyte from the matrix prior to measurement or by using appropriate chemistry to overcome matrix interferences. In the modern laboratory the analysis is almost invariably instrument based but the instrumental determination is often the final step of a complex analytical method involving extensive pretreatment of the sample. Hence, calibration of the instrument using a pure chemical standard, even a traceable one, is on its own insufficient to achieve reliable and comparable results. The sample matrix problem has stimulated the development of two pragmatic solutions: matrix reference materials and interlaboratory comparisons. The matrix-matched, certified reference material (CRM) is a unique type of chemical standard commonly used to validate complete measurement methods and sometimes for instrumental calibration (e.g., in XRF). Such standards must be available for each required analyte/matrix combination. Similarly, interlaboratory comparisons are undertaken for each relevant analyte/matrix combination in order to establish comparability of data between laboratories. These comparisons range from round robin studies, which collaboratively test a new method, to formal PT schemes that assess agreement between laboratories on an ongoing basis. CRMs and PT schemes have been used by analysts with reasonable success over many years but they both have a number of technical, practical, and economic limitations. The need for a wide variety of application-specific CRMs has lead to fragmented production without any formal relationship between the certified values of CRMs produced for different applications or by different organizations. There are thousands of CRMs in use but many of those required for critical applications such as manufacturing, trade, health, or the environment are unavailable. In addition, production costs are high and it is difficult or impossible to manufacture sufficiently stable CRMs for some applications. Interlaboratory comparisons also have a number of limitations, particularly that they are time-consuming and expensive. Comparability usually extends only to the immediate participants in a single comparison because comparability between different comparisons is rarely established, even when they are coordinated by the same organization. It is impracticable to organize comparisons for every routine application or to organize a worldwide comparison involving all the laboratories requiring comparability for each measurement application. These problems have long been recognized as a significant technical and economic limitation in
delivering sound chemical analysis data. The situation is steadily worsening with increasing demand from purchasers of data and by regulators for proven comparability of measurements. This is for several reasons. Global expansion of trade, which means more countries and more laboratories need to be brought into each interlaboratory comparison. In addition, increasing numbers of measurements are used in support of regulations, for which there is an expanding requirement for rigorously proven reliability and comparability. Finally, increasing use of subcontracted measurements, due to commercial pressures on laboratories, requires not only conformity of contractors to quality systems but also demonstration of the comparability of data from different contractors. To ensure reliable and comparable chemical measurements in the twenty-first century, it is desirable to have in place a unified international system based on the traceability of measurement results.
Achieving Traceability in Analytical Chemistry Traceable chemical measurement results require a measurement infrastructure analogous to the systems that underpin physical measurements, as described above. Chemical measurements have developed more or less on a sectorial basis and in a different culture, so that the systems developed for physical measurements cannot easily be directly applied to chemical or, indeed, biological measurements. In most countries, expertise in chemical metrology is also more widely dispersed than is the case for physical measurements, which are mainly focused on a single national measurement institute. Traceable measurements also require that the uncertainty of the entire chemical measurement procedure is fully understood. The uncertainty of the sample preparation and pretreatment is, however, largely an empirical estimate and the uncertainty associated with taking the initial sample or subsample is often overlooked. Developing reference methods that offer improved and rigorously determined levels of uncertainty for difficult sample matrices is a key factor in solving this problem. In order to address both the technical and organizational problems, the CIPM (see Figure 1) decided in 1993 to establish an international, collaborative program of work in chemistry. This program is organized through the CIPM’s Comite´ Consultatif pour la Quantite´ de Matie`re (CCQM) – the committee for metrology in chemistry. The CCQM’s task is to resolve the practical difficulties of achieving comparable chemical measurements through traceability and to provide an international structure of
QUALITY ASSURANCE / Traceability 483
chemical laboratories. These laboratories are signatories to the BIPM MRA (see above) and are required to demonstrate the equivalence of their measurement data through measurement comparisons as well as implementing a quality management system for their calibration or measurement certificates. Once this has been done, claims may be submitted by each institute listing its measurement capabilities, i.e., standards or calibration services that it provides. These are vetted by peer review before inclusion in the BIPM Key Comparison Database. The CCQM has organized an ongoing series of key comparisons that reflect important applications relevant to industry, trade, health, and the environment, not just measurements on single-substance calibration standards. An example of some of the current CCQM entries in the BIPM database can be seen in Figure 4. The results for one such Key Comparison, CCQMK13, listed in Figure 4, are shown in Figure 5. This example illustrates a trace analysis application, the determination of lead in a sediment. The error bars
represent the expanded uncertainty reported by each participating national measurement institute. Bearing in mind that this is a difficult trace determination, these uncertainties and the degree of equivalence between the individual results (shown on the y-axis) illustrate how the participating institutes are working at the limits of current analytical methodology. This is necessary because, in order to underpin internationally traceable measurements, data from these laboratories form the ultimate reference points for calibration chains that end with routine measurements by field laboratories. Each calibration stage in such a chain introduces an increase in the uncertainty of the resulting measurement. Hence, unless the calibration chains can be kept very short, the national measurement institutes must achieve uncertainties substantially smaller than those needed by the field laboratories. As mentioned above, the BIPM Key Comparison Database provides access to the measurement capabilities of these institutes. Each such entry shows the dissemination range in terms of both the available concentration range and the
Key and supplementary comparisons Search criteria: amount of substance, inorganics your request produced 11 result(s) List of comparisons Click on a comparison identifier to view more CCQM-K2 Comparison type, Field Status CCQM-K8 Comparison type, Field Status CCQM-K13 Comparison type, Field Status CCQM-K14 Comparison type, Field Status CCQM-K24 Comparison type, Field Status
Page 1 2 3
Cadmium and lead in natural water 1998 Key comparison in amount of substance, inorganics Approved for equivalence, Results available Monoelemental calibration solutions of Al, Cu, Fe, and Mg 1999−2000 Key comparison in amount of substance, inorganics Approved for equivalence, Results available Amount content of cadmium (Cd) and lead (Pb) in sediment 2000 Key comparison in amount of substance, inorganics Approved for equivalence, Results available Calcium in human serum 2003 Key comparison in amount of substance, inorganics Measurements completed Cadmium (Cd) in rice 2001 Key comparison in amount of substance, inorganics Approved for equivalence, Results available
Figure 4 Part of a table taken from the BIPM Key Comparison Database (KCDB) which may be viewed on the BIPM website (www.bipm.org). The table shows some of the chemistry key comparisons organized by the working groups of the CCQM. (Reproduced with permission from BIPM website.)
484 QUALITY ASSURANCE / Traceability CCQM–K13: Lead in sediment, amount content ~170 µmol kg –1
Degrees of equivalence (µmol kg –1)
10
5
0
–5
–10 Uncertainty bars shows with coverage factor of 2 VNIIM
PTB
NRCCRM
NRC
NIST
NIMC
NARL
BNM–LNE
LGC
KRISS
IRMM
CSIR–NML
CENAM
BAM
–15
Figure 5 Results of one of the key comparisons listed in the BIPM Key Comparison Database, CCQM-K13, which concerns the determination of lead in sediment samples at trace levels. This information may be viewed on the BIPM website (www.bipm.org). (Reproduced with permission from BIPM website.)
Calibration and measurement capabilities Sediments, soils, ores, and particulates United Kingdom, LGC (Laboratory of the Government Chemist) Complete CMCs in Amount of substance for sediments, soils, ores, and particulates for United Kingdom (.pdf file) Dissemination range of measurement capability Analyte or Matrix or Mass fraction in Relative expanded uncertainty in component material µg per g % Lead 30–90 2–3 Sediment Figure 6 An example of a measurement capability (CMC) submitted for international peer review and accepted for inclusion in the BIPM Key Comparison Database. This example shows a relevant CMC for one of the institutes that participated in CCQM-K13 (illustrated in Figure 5). The database presently comprises several thousand CMCs, including a wide range of chemical measurements. (Reproduced with permission from BIPM website.)
corresponding range of measurement uncertainty. A typical CMC entry from one institute, for the capability tested by CCQM-K13, is shown in Figure 6.
Traceability and Measurement Uncertainty It should be clear from the above discussion that, regardless of the availability of standards, reference materials or calibration services having reference values exhibiting international traceability, the results dependent on them will not be traceable unless field laboratories are able to obtain reliable estimates of their own measurement uncertainty. This is, in fact, a requirement for accreditation to ISO 17025 but the practical difficulties of achieving it for
chemical measurements are considerable. It is well known that the uncertainties of analytical results are often large because many analytical methods require several quite complex operations (e.g., extraction, clean-up, or preconcentration) prior to the final measurement using a calibrated instrument. The uncertainty associated with these stages is frequently difficult, or sometimes impossible, to quantify and the analyst must resort to an estimate based on the available data and previous experience. Nevertheless, it is essential that laboratories strive to achieve the best possible estimate of uncertainty at the method validation stage. A key factor in this regard is the availability of appropriate matrix reference materials. In order to achieve routine results that are both reliable and traceable, it is essential that
QUALITY ASSURANCE / Accreditation 485
validation is based on materials that are both similar to the routine samples and have reference values with substantially smaller uncertainties than is required for routine data. Of equal importance is developing a base of knowledge and expertise that can help laboratories to resolve some of the problems encountered in evaluating the uncertainties of analytical results. Achieving these goals will not happen overnight but adopting the twin principles of measurement traceability and uncertainty offers analytical scientists a route map by which they may be achieved.
Acknowledgments The diagrams illustrating the international measurement system and the examples from the BIPM Key Comparison Database were provided by the Bureau International des Poids et Mesures, Se´vres, France, and are reproduced with their permission. See also: Quality Assurance: Reference Materials; Method Validation.
Further Reading EN-ISO/IEC 17025:2000 (2000) Requirements for the Competence of Testing and Calibration Laboratories. Geneva: International Standards Organisation. EURACHEM (1998) The Fitness for Purpose of Analytical Methods: A Laboratory Guide to Method Validation and
Related Topics. Available from the EURACHEM website (http://www.eurachem.ul.pt). EURACHEM (2000) Quantifying Uncertainty in Analytical Measurements, 2nd edn. Available from the EURACHEM website (http://www.eurachem.ul.pt). EURACHEM (2002) The Selection and Use of Reference Materials; A Basic Guide for Laboratories and Accreditation Bodies, EEE/RM/062. Available from the EURACHEM website (http://www.eurachem.ul.pt). EURACHEM/CITAC (2002) Guide to Quality in Analytical Chemistry. Available from the EURACHEM (http:// www.eurachem.ul.pt) or CITAC (http://www.citac.cc) websites. EURACHEM/CITAC (2003) Traceability in Chemical Measurement, A Guide to Achieving Comparable Results in Chemical Measurement. Available from the Eurachem website (http://www.eurachem.ul.pt). International Organization for Standardization (ISO) (1995) Guide to the Expression of Uncertainty in Measurement. Geneva: ISO. ISO (1993) International Vocabulary of Basic and General Terms in Metrology. Geneva: International Standards Organization. McNaught AD and Wilkinson A (1997) IUPAC Compendium of Chemical Terminology, 2nd edn. Cambridge, UK: Royal Society of Chemistry. Stoeppler M, Wolf WR, and Jenks PJ (2000) Reference Materials for Chemical Analysis. New York: Wiley-Interscience. Taylor JK (1993) Handbook for SRM Users, NBS Special Publication 260-100. Gaithersburg: National Institute of Standards and Technology.
Accreditation E J Newman, Newman, Bucknell Associates, Wimborne, UK & 2005, Elsevier Ltd. All Rights Reserved.
Introduction One indication of the importance of analytical chemistry is that it has been estimated that B3% of the gross domestic product of the more advanced industrial nations is spent on analytical testing. Other indications of importance come from major areas of application of analytical science, such as: food safety, drinking water quality, animal feeds, fertilizers and pesticides; air and coastal water quality monitoring, workplace health and safety monitoring, and applications to the environment generally. Also applications in the field of health care including the quality control (QC) of pharmaceuticals, and clinical analyses for both diagnosis and to monitor the effects of
therapy; the wide area of forensic science in which analytical chemistry is a core subject; and the many and varied important industries not included in the above, in which analysis provides vital QC, and which range from the long-established, such as steelmaking or dyeing, to the modern manufactures of microprocessors, optical fibers, and other advanced materials. To meet all these and many other demands, analysts produce, as a conservative estimate, over a billion items of analytical data every year in the United Kingdom alone. It is clear from this that analytical data provide the basis for thousands of important, even critical, decisions every day of the year. Furthermore, the importance of chemical analysis is increasing as legislators, considering scientific evidence, much of which was itself derived from analytical chemistry, continue to frame regulatory requirements, which can be enforced only by the endeavors of skilled analysts.