A framework for the application and materials in analytical chemistry

 Working group 5 of EuraChem Nederland has developed a framework for the implementation of reference materials in analytical chemistry. In this discussed paper, the framework is proposed as a tool for the development of standard operation procedures (SOPs) in laboratories. The implementation of (certified) reference materials in these SOPs is of major importance in establishing comparability and traceability in measurement results, which in turn play a crucial role in measurement in support of trade, environmental issues, and characterisation of materials. Recent developments in the field of uncertainty analysis require the application of reference materials. It is recognised that the calculation of the combined measurement uncertainty becomes almost impossible without the use of certified reference materials with a stated uncertainty. Received: 1 December 1995 Accepted: 20 December 1995     

Clinical reference materials for the validation of the performance of photometric systems used for clinical analyses

 There are a wide variety of spectrophotometric devices nowadays used in health services with various qualities of manufacture methods of measurement and metrological characteristics for performing the necessary measurements. Therefore, to meet the accuracy and repeatability requirements needed in medical diagnosis and treatment, the validation of the performance of such systems by clinical chemistry laboratories is essential. However, the validation of a spectrophotometric system for clinical analyses requires several reference materials, according to the end use of the measurement results. This paper discusses some characteristics required of the clinical reference materials needed and used by Romanian Institute of Metrology for validation work. Types of clinical reference materials developed in the national area for this purpose are also presented. Received: 23 April 1997 · Accepted: 7 July 1997     

Traceability of (values carried by) reference materials

 Traceability is a property of the result of a measurement. Since values carried by (reference) materials must also have been obtained, of necessity, by measurement, the definition of traceability also applies to reference materials. It is extremely helpful to give the traceability (of the origin) of a reference material a separate name, i.e. 'trackability'. An analysis of the function of values carried by reference materials, shows that they can fulfill different functions, depending on the intended use. One of the functions located outside the traceability chain – and hence not very relevant for establishing traceability – is evaluating the approximate size of the uncertainty of the measurement of an unknown sample by performing a similar measurement on a reference material, used as a 'simulated sample'. Another function is located inside the traceability chain, where the reference material is used as an added 'internal standard'. Then, the value carried by the reference material is essential for establishing the traceability of the measured value of an unknown sample. In the latter application, the reference material acts as an 'amount standard' (the certified value for amount is used). Received: 11 November 1999 / Accepted: 24 February 2000     

Bioanalytical method validation and its implications for forensic and clinical toxicology – A review

The reliability of analytical data is very important to forensic and clinical toxicologists for the correct interpretation of toxicological findings. This makes (bio)analytical method validation an integral part of quality management and accreditation in analytical toxicology. Therefore, consensus should be reached in this field on the kind and extent of validation experiments as well as on acceptance criteria for validation parameters. In this review, the most important papers published on this topic since 1991 have been reviewed. Terminology, theoretical and practical aspects as well as implications for forensic and clinical toxicology of the following validation parameters are discussed: selectivity (specificity), calibration model (linearity), accuracy, precision, limits, stability, recovery and ruggedness (robustness). Received: 16 June 2002 Accepted: 12 July 2002 Part of this review was published in the communications of the International Association of Forensic Toxicologists (TIAFT; TIAFT Bulletin 32 (2002): 16–23) and of the Society for Forensic and Toxicologic Chemistry (GTFCH; Toxichem and Krimitech 68 (2001): 116-126). Correspondence to F. T. Peters     

The NATA scheme for accreditation of certifiers of reference materials

 Certified reference materials are widely used for the calibration of measuring equipment and for the evaluation or validation of measurement procedures. The use of reference materials makes possible the transfer of the values of measured or assigned quantities between testing, analytical and measurement laboratories, both nationally and internationally. There is an increasing number of reference materials producers in other countries, and a demonstration of their scientific and technical competence is now more widely considered to be a basic requirement for ensuring the quality of reference materials. This article outlines recent activities by international bodies and their culmination in a scheme of accreditation of certifiers of reference materials which has been developed by the National Association of Testing Authorities, Australia (NATA).     

Some aspects of the evaluation of measurement uncertainty using reference materials

 In practice there are three aspects that need to be considered in order to achieve the required traceability according to its definition: the 'stated reference', the 'unbroken chain of calibrations' and the "stated uncertainty". For a certain chemical result, each of these aspects highly depends on the measurement uncertainty, both on its magnitude and how it was estimated. Therefore, the paper describes the experience of the Romanian National Institute of Metrology in estimating measurement uncertainty during the certification of reference materials (RMs), in metrological activities (calibration, pattern approval, periodical verification, etc.), as well as during the analytical measurement process. Practical examples of estimation of measurement uncertainty using RMs or certified reference materials are discussed for their applicability in spectrophotometric and turbidimetric analysis. Use of the analysis of variance to obtain some additional information on the components of measurement uncertainty and to identify the magnitude of individual random effects is described. Received: 12 November 1999 / Accepted: 25 February 2000     

Implementing the GUM in the certification of reference materials: the revision of ISO Guide 35

The availability of certified reference materials, certified in accordance to the GUM is an important tool for the proper estimation of measurement uncertainty in routine analysis. Many CRMs may suffer from incomplete or wrongly estimated uncertainties, mainly due to lack of guidance on how to implement the GUM in the production of CRMs. In particular the inclusion of the impact of inhomogeneity and instability in the uncertainty budget is often missing. The ongoing revision of ISO Guide 35 aims to fill this gap in providing guidance how (batch) inhomogeneity and instability can be translated into measurement uncertainty. The structure of the current ISO Guide 35 has been maintained as far as possible, but major parts underwent revision to become better aligned with GUM and ISO Guide 34 (2000). Received: 9 April 2001 Accepted: 22 October 2001     

Twenty-five years of international collaboration in reference materials via ISO/REMCO

This paper looks back on a quarter century of history of the Council Committee on Reference Materials of the International Organization for Standardization – REMCO. It begins however with the period before its formation in 1976 to describe how the Committee came into being as a response to a growing need by the analytical community for the number and variety of reference materials (RMs) as well as a need for the assurance of the quality of RMs and ends with a view of REMCO activities in the near future. This is not intended as a detailed history but instead to describe the evolution of REMCO by identifying major activities and accomplishments of REMCO. Received: 21 January 2002 Accepted: 22 January 2002     

Uncertainty calculations in the certification of reference materials

To serve as a measurement standard, a (certified) reference material must be stable. For this purpose, the material should undergo stability testing after it has been prepared. This paper looks at the statistical aspects of stability testing. Essentially, these studies can be described with analysis of variance statistics, including variant regression analysis. The latter is used in practice for both trend analysis and for the development of expressions for extrapolations. Extrapolation of stability data is briefly touched upon, as far as the combined standard uncertainty of the reference material is concerned. There are different options to validate the extrapolations made from initial stability studies, and some of them might influence the uncertainty of the reference material and/or the shelf-life. The latter is the more commonly observed consequence of what is called ’stability monitoring’. Received: 6 October 2000 Accepted: 4 December 2000     

Traceable property values of in-house reference materials

The traceability of in-house reference materials (IHRM) is discussed. It is shown that a systematic error in results of a measured value, specific to a measurement method or to a laboratory developing an IHRM, can be overcome if a comparative approach to IHRM characterization is used. A traceability chain of the value carried by the IHRM to the value carried by the reference material with higher metrological status and sufficiently similar matrix (for example, a certified reference material – CRM according to ISO Guide 30) is helpful in such a case. The chain is realized when the IHRM samples are analysed simultaneously with the CRM samples under the same conditions. This and other traceability chains necessary for the IHRM development are examined as the measurement information sources.     

Reference materials in environmental trace organic analysis

 The paper reviews the application of reference materials (RMs) in environmental analysis of trace organic pollutants. The problems related to RM preparation, stability, use, etc. are critically discussed. Importance of analytical quality assurance and the role RMs play in the process are emphasised. Received: 18 May 1999 · Accepted: 27 December 1999     

Measurement principles for traceability in chemical analysis

 By the definition of the mole as a base unit for amount-of-substance measures within the International System of Units (SI), chemists can make chemical measurements in full compliance with established metrological principles. Since the mole requires exact knowledge of the chemical entity, which is often neither available nor of practical relevance to the purpose of the measurement, the SI units of mass or length (for volume) are unavoidable in the expression of results of many chemical measurements. Science, technology, and trade depend upon a huge and ever increasing number and variety of chemical determinations to quantify material composition and quality. Thus, international harmonization in the assessments of processes, procedures, and results is highly desirable and clearly cost effective. The authors, with relevant experience and responsibilities in Europe and America, have found some consensus in the interpretation of the metrological principles for chemical measurements, but believe open discussion should precede wide implementation by chemical communities. In fostering this dialogue, this paper shows, for instance, that more precise interpretation of the definitions for "traceability," "calibration," and "validation" is needed for present-day chemical measurements. Problems that face scientists in making measurements do not all vanish just by adherence to the SI. However, such compliance can improve communication among chemists and metrologists. Received: 30 June 1995 Accepted: 30 June 1995     

Uniform oligomers as reference materials for molecular weight determination of polymers

 Uniform oligomers are special oligomers having no molecular weight distribution. They have been used as reference materials for polymer characterization, especially for accurate molecular weight determination in lower molecular weight ranges. These oligomers are used for different purposes. First, they are used in the calibration for chromatographic or spectroscopic data. Second, they are applied to identifying peaks appearing in chromatographies such as supercritical fluid chromatography (SFC) of oligomeric mixtures. Finally, they could give accurate instrumental or physicochemical constants used in polymer characterizations. The uniform oligomers have been prepared by using preparative chromatographies as separation methods. In some cases, step-wise syntheses have been applied together with the chromatographic methods. Recently, we prepared uniform oligostyrenes and oligo(oxyethylene)s whose molecular weights are greater than 1000 by using preparative size exclusion chromatography. More recently, using preparative SFC, some Japanese researchers have prepared high molecular weight and uniform oligomers such as oligo(methylmethacrylate)s. In this article, we briefly review recent progress mainly made by Japanese researchers in the field of preparation, analysis and applications of these pure oligomers. Received: 20 September 1996 Accepted: 3 December 1996     

Reference materials for large-scale metal deposition surveys

 In order to ensure quality assurance in large-scale environmental contamination studies involving many different analytical laboratories, the use of calibrated reference materials is essential. Prior to a survey of atmospheric metal deposition in 1995 comprising 20 countries and covering large parts of Europe, the lack of suitable reference materials of moss and organic-rich soil was apparent. In order to improve the quality of analytical data to be produced in this international survey, candidate analytical laboratories were invited to participate in an intercomparison exercise. Three moss and three soil humus reference samples specifically prepared for this purpose were distributed anonymously among the laboratories, which were asked to report data for ten priority elements (V, Cr, Fe, Ni, Cu, Zn, As, Cd, Hg, Pb) and as many additional elements as they determined normally. In this paper the analytical data from the intercomparison are evaluated, and recommended values for the ten priority elements and 17 additional elements (B, Na, Mg, Al, S, K, Ca, Mn, Co, Se, Rb, Sr, Sb, Cs, Ba, La, Th) in each of the six reference samples are established. These samples should be useful for similar future studies including areas where the contamination levels are very low. Received: 17 October 1996 Accepted: 2 January 1997     

Accreditation system for reference material producers and certified reference materials for iron and steel in Japan

  ISO 9000 series strictly requires traceability to national or international measurement standards. It is becoming more necessary to make clear the concept of traceability of measurement standards with respect to chemical composition and to accredit the reference material producers. In Japan, the accreditation system for reference material producers is considered to satisfy the requirement of ISO Guide 34, ISO 9000 series and ISO/IEC Guide 25, while the producer fulfills the concept of traceability of measurement standards. This paper describes the production of iron and steel reference materials in Japan relating to the international standardization of methods (written standards) and accreditation of reference material producers. Received: 11 October 1996 Accepted: 5 December 1996     

The establishment of an Australian National Analytical Reference Laboratory (NARL)

 The National Analytical Reference Laboratory (NARL) was established by the Commonwealth Government within the Australian Government Analytical Laboratories (AGAL) Public Interest Programme in 1997, to help provide Australian scientists with the chemical standards they need to make reliable measurements. Reliable chemical measurements are vital to many aspects of our social and economic life including public health, environmental control, industrial productivity, trade innovation and government regulation. Mutual recognition of measurement results and the avoidance of costly disputes require the development of a structured and common system of measurement. Working-level measurements should be directly linked to national standards, which are themselves interlinked through international comparisons. Although metrology in chemistry is still in its infancy, increasing numbers of countries are establishing facilities to serve both national needs and to contribute to the international measurement system. The aim at NARL is to lead the development of an Australian chemical measurement system, which is harmonized with similar systems in other countries. This paper was presented at the Co-operation on Traceability in Analytical Chemistry (CITAC) symposium on Analytical Quality Assurance for the Twenty-first Century, held in Sydney on 15–16 October 1998. It describes the rationale for establishing NARL, the process of getting it started, the positioning, aims and strategy of NARL, the development of its work programme and plans for both national and international collaboration. If you would like more information or would like to contribute to the work of NARL please contact us at the above address.     

Qualification and validation of software and computer systems in laboratories

 Installation and operational qualification are important steps in the overall validation and qualification process for software and computer systems. This article guides users of such systems step by step through the installation and operational qualification procedures. It provides guidelines on what should be tested and documented during installation prior to routine use. The author also presents procedures for the qualification of software using chromatographic data systems and a network server for central archiving as examples. Received: 31 October 1997 · Accepted: 25 November 1997     

Qualification and validation of software and computer systems in laboratories

 Existing software and computer systems in laboratories require retrospective evaluation and validation if their initial validation was not formally documented. The key steps in this process are similar to those for the validation of new software and systems: user requirements and system specification, formal qualification, and procedures to ensure ongoing performance during routine operation. The main difference is that frequently qualification of an existing system is based primarily on reliable operation and proof of performance in the past rather than on qualification during development and installation. Received: 30 April 1998 · Accepted: 2 June 1998     

Qualification and validation of software and computer systems in laboratories

 Software and computer systems are tested during all development phases. The user requirements and functional specifications documents are reviewed by programmers and typical anticipated users. The design specifications are reviewed by peers in one to two day sessions and the source code is inspected by peers, if necessary. Finally, the function and performance of the system is tested by typical anticipated users outside the development department in a real laboratory environment. All development phases including test activities and the final release follow a well-documented procedure. Received: 17 May 1997 · Accepted: 30 June 1997     

Accreditation of reference material producers

 The use of reference materials is the most pragmatic means by which the analyst can achieve comparability of data. Reference material producers therefore need to have adequate quality systems in place for ensuring the reliability of their materials. In order to provide guidance to both producers and assessors, ISO Guide 34 has recently been produced detailing the quality system requirements for the production of reference materials. CITAC, REMCO and ILAC are now collaborating in the revision of this guide to produce a free-standing document detailing the general requirements for the competence of reference material producers. This paper discusses some of the more important issues described in these documents. The possible formation of an international register containing details of a reference material producer's quality system status is also discussed.