k0-NAA, a valuable tool for reference-material producers

The main concern of producers of certified reference materials (CRM) is the preparation of high-quality products with demonstrated homogeneity and stability, combined with a well established set of certified characteristics. CRM producers must, furthermore, comply with other constraints imposed by the ISO Guide 34: ·*production processes, production control, and certification analyses should be performed by expert laboratories, using validated protocols documented in their respective quality assurance manuals; ·*laboratory mean values and the corresponding “expanded” uncertainties, must be used for the determination of the certified values, as recommended by the ISO Guide to the Expression of Uncertainties in Measurements (GUM); and ·*when possible, traceability of the certified value to the SI units, using appropriately validated and/or primary methods, must be ensured. k₀-NAA, i.e. neutron activation analysis with k₀ standardization, is one of the analytical techniques implemented at the Reference Material Unit of IRMM; it meets the first two requirements.     

Estimating the uncertainty of stability for matrix CRMs.

The new version of ISO Guide 34 requires producers of certified reference materials (CRMs) to include contributions of possible instability to the overall CRM uncertainty, to obtain a value for the uncertainty in compliance with the Guide to the Expression of the Uncertainty in Measurement (GUM). A pragmatic approach to estimating the uncertainty of stability is presented. It relies on regression analysis of stability data with subsequent testing of the slope of the regression line for significance. If the slope is found to be statistically insignificant, a shelf life is chosen and the uncertainty connected with this time is estimated via the standard deviation of the slope. This uncertainty is included in the overall uncertainty of the CRM. This approach is explained with examples showing its applicability to matrix CRMs.     

Estimating the uncertainty of stability for matrix CRMs

The new version of ISO Guide 34 requires producers of certified reference materials (CRMs) to include contributions of possible instability to the overall CRM uncertainty, to obtain a value for the uncertainty in compliance with the Guide to the Expression of the Uncertainty in Measurement (GUM). A pragmatic approach to estimating the uncertainty of stability is presented. It relies on regression analysis of stability data with subsequent testing of the slope of the regression line for significance. If the slope is found to be statistically insignificant, a shelf life is chosen and the uncertainty connected with this time is estimated via the standard deviation of the slope. This uncertainty is included in the overall uncertainty of the CRM. This approach is explained with examples showing its applicability to matrix CRMs. Received: 12 October 2000 / Revised: 2 January 2001 / Accepted: 3 January 2001     

The work of ISO-REMCO’s accreditation task group

This paper discusses some of the work of ISO-REMCO’s Task Group 4 (TG4) – the Accreditation TG, giving firstly a brief account of the recently published ISO Guide 34 – which gives guidance on the type of quality system a reference material producer should have in place. Secondly, work on the future development of Guide 34 to produce a document against which it will be possible for producers to be accredited without reference to ISO Guide 25 is discussed, and thirdly, the possible formation of an international register of CRM producers, which will provide users with information about the quality status of different producers, is considered.     

Development of a reference material for residues of chlorfluazuron and fluazuron in beef fat ACSL CRM 3

The certification by interlaboratory testing of a candidate reference material (ACSL CRM 3) for the concentration (mass fraction) of the pesticides chlorfluazuron (CFZ) and fluazuron (FZN) is described. The certification process was based on a two-stage nested design described in ISO Guide 35. Analysis of results reported by collaborating laboratories provided an assessment of the homogeneity of the RM. The certified values were chlorfluazuron -1.01 mg/kg and fluazuron -1.02 mg/kg. The upper and lower 95% confidence limits for CFZ and FZN were calculated to be: CFZ upper=1.05 mg/kg, lower=0.97 mg/kg; FZN upper=1.08 mg/kg, lower=0.95 mg/kg. A certificate was prepared according to guidelines set out in ISO Guide 31.     

Accreditation of reference material producers: Let's get it right!

The accreditation of testing and calibration laboratories to ISO/IEC 17025 is increasingly calling for the accreditation of reference material (RM) producers. Two international guides, ISO Guide 34 (2000) " General requirements for the competence of reference material producers" issued by the ISO Committee on Reference Materials and ILAC-G 12 " Guidelines for the requirements for the competence of reference material producers" issued by the International Laboratory Accreditation Cooperation (ILAC), are already in use for this purpose. Recently however initiatives have been launched to accredit RM producers to ISO 17025 as calibration laboratories and it has been suggested that a combination of ISO/IEC 17025 " General requirements for the competence of testing and calibration laboratories" and ISO Guide 34 may be the best option. This publication is an expression of the position of the ISO Committee on Reference Materials (ISO/REMCO) on the standards and guides currently in use in the accreditation of RM producers. The paper discusses the advantages and disadvantages of these standards and guides from the perspective of benefit to RM producers and RM users. In conclusion, the use of ISO Guide 34 alone or in combination with ILAC-G 12 is the preferred system for the accreditation of RM producers. Therefore ISO/REMCO strongly encourages all accreditation bodies to adopt ISO Guide 34.     

Consideration of the uncertainty in the CRM value with the analysis of solid materials using atomic spectrometry

 The principles of the ISO "Guide to the expression of uncertainty in measurement" are applied to the analysis of solid materials by graphite furnace atomic absorption spectrometry. Assessment of trueness is achieved by the analysis of a certified reference material (CRM) under fixed instrumental conditions. For the evaluation of the method's uncertainty (as part of the validation) a model equation is derived, considering all significant contributions, including the uncertainty in the CRM value and the uncertainty in the CRM analysis. A concrete example is presented and discussed (soya flour as an unknown sample and CRM BCR rye grass). For routine analysis a pooled estimate from the validation experiment can be used, leading to an acceptable small uncertainty range even in the case of "duplicate determination". The test for trueness (acceptance) of the result of the CRM analysis is applied and the correction for detected bias is discussed. Received: 28 June 1998 · Accepted: 13 July 1998     

The view of IRMM on accreditation of CRM producers

This article describes the views of IRMM on accreditation of CRM producers and the philosophy which is behind these views. More specifically, it explains the reasons for choosing ISO Guide 34 rather than ISO/IEC 17025 as the basis document for the proposed accreditation of its CRM activites. Received: 27 May 2002 Accepted: 11 July 2002 Acknowledgements Information on accreditation programmes in Australia and USA provided by Maree Stuart (NATA) and Randall V. Querry (AL2A) is greatly acknowledged. Correspondence to J. Pauwels     

Evaluation of the stability of ethanol in water certified reference material: measurement uncertainty under transport and storage conditions

This study simulated the transport and storage conditions of ethanol in water certified reference material (CRM) produced by the Chemical Metrology Division of Inmetro—DQUIM with the purpose of estimating the measurement uncertainty related to stability. The short-term stability study was performed on five different mass fractions (w) in terms of mg ethanol/g solution of the ethanol in water CRM. The nominal values are w = 0.5, 0.9, 1.1, 3.8 and 4.6 mg/g, at temperatures of 4 and 60 °C. On the other hand, the long-term stability study was developed on four different mass fractions (nominal values): w = 0.5, 0.9, 1.1 and 4.6 mg/g, at a temperature of 20 °C. This paper will show the data from the long-term stability study that took place over 52 weeks. The method used complies with ISO Guide 35, the BCR Guideline for Feasibility Studies and ISO Guide 34. According to the statistical parameters used in both studies, the stability of ethanol in water CRM was confirmed for all of the mass fractions studied.     

Application of mycotoxin RM's in method development and quality assurance

Summary New analytical methodology for determining aflatoxin M₁ in milk has been validated using the Eurpean Community Bureau of Reference (BCR) aflatoxin M₁ in powdered milk certified reference material (CRM). Good agreement with the certified values for aflatoxin M₁ were obtained using an immunoaffinity column clean-up procedure for the preparation of milk samples. This demonstrated the validity of this novel approach. Similarly, using the CRM's a fully automated sample handling procedure utilising robotics was validated for making routine aflatoxin determinations. The use of CRM's has now become part of the normal quality assurance procedure for survey work for aflatoxin M₁ in milk, and CRM's are analysed blind for every 15 survey samples.The need for additional mycotoxin CRM's in foods and animal feeds is discussed in relation to existing European Regulations, and the needs for intercomparison of surveillance data. Preliminary work under the BCR programme is outlined concerning the preparation of a 4-deoxynivalenol calibrant solution, and the certification of cereals containing this Fusarium mycotoxin.

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Anwendung von Mycotoxin-Referenzmaterialien zur Methodenentwicklung und Qualitätssicherung

     

Development of a certified reference material for cachaça: an effective material for quality assurance

Cachaça is the typical and genuine denomination for the sugar cane beverage produced in Brazil. It has an alcoholic content between 38 and 48 % by volume, at 20 °C, and is obtained from the distillation of fermented sugar cane juice with the possible addition of up to 6 g/L of sugar, expressed by sucrose. This paper aims to outline the approach taken for the certification of the mass fraction of individual alcohols and their associated uncertainties in a cachaça certified reference material (CRM) produced by the Organic Analysis Laboratory of the Chemical Metrology Division of Inmetro. The requirements of ISO Guide 31, ISO Guide 34 and ISO Guide 35 were followed for the certification. This included the assessment of the degree of homogeneity of the material, the short-term stability study to determine the transport conditions, the long-term stability study to establish the shelf life and storage conditions of the CRM and the characterization process. The certified values were determined by two analytical techniques: gas chromatography coupled to mass spectrometry and gas chromatography with flame ionization detection. In order to support the routine testing of cachaça, in helping analytical laboratories validate and standardize their methods, the certified reference material (CRM 02.1/10.003b) was developed and certified for the mass fractions of methanol (9.18 mg/100 g ± 0.82 mg/100 g), 2-butanol (4.15 mg/100 g ± 0.40 mg/100 g), 1-butanol (1.30 mg/100 g ± 0.18 mg/100 g), isobutanol (24.0 mg/100 g ± 1.0 mg/100 g) and 1-propanol (29.4 mg/100 g ± 1.3 mg/100 g) in a spiked cachaça.     

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.     

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     

Evaluation of uncertainty of reference materials

 Certification of reference materials is far more than just characterisation of a selected homogeneous batch of material. From the perspective of the ISO Guide on the Expression of Uncertainty in Measurement (GUM) all uncertainty sources relevant to the user of an individual certified reference material (CRM) sample at a moment in time should be part of the CRM uncertainty. This not only includes the full uncertainty of the batch characterisation (rather than the statistical variation), but also all uncertainties related to possible between-bottle variation, instability upon long-term storage and instability during transport to the customer. Received: 21 April 1999 · Accepted: 24 September 1999     

Laboratory accreditation in Italy for reference solution production of sucrose in water

The accreditation of Chemifarm srl laboratory for the calibration of two characteristics on the same aqueous solution has been achieved. The process has been executed by the Italian accreditation body for calibration laboratories (SIT). This is the first example of a producer of certified reference solutions in Italy. The solutions are mixtures of sucrose in water at several concentrations and are characterised for refractive index in the range of 1.33299 to 1.38115 and for mass fraction of sucrose in the range of 0 to 30 (commercially expressed in Brix degrees). Both traceability paths, obtained through refractometric and gravimetric methods, are reported. Furthermore, the paper describes the approach adopted to match the criteria based on ISO Guide 34 and ILAC-G 12, the documents with requirements for certified reference material producers, in compliance with those of ISO/IEC 17025, the norm for the laboratory accreditation.     

Development of clenbuterol reference materials: lyophilized bovine eye samples free of clenbuterol (CRM 673) and containing clenbuterol (CRM 674)

The certification by inter-laboratory testing of two candidate reference materials (RMs) for the mass concentration of the anabolic agent clenbuterol in bovine eye material is described: RM 674 with ca 10 microg clenbuterol per kg of eye matrix and RM 673 clenbuterol-free eye matrix as the negative control (<0.50 microg kg(-1)). Both candidate RMs were certified by eleven EU laboratories, and sixty-six accepted replicate measurements were included in the "Certification Study". The precision of the measurement process was assessed by calculation of the standard variation determined within each laboratory during the certification step. The study was performed according to the "Guidelines for the production and certification of BCR reference materials" and to "ISO guide 31, 33, and 35". The certified clenbuterol mass concentration for clenbuterol-free eye material CRM 673 (calculated on the basis of clenbuterol as the free base) was <0.50 microg kg(-1). The corresponding concentration for clenbuterol-containing eye material CRM 674 was 9.42 +/- 0.88 microg kg(-1). These certified values are very close to the desired target concentration of <0.5 microg kg(-1) and ca 10 microg kg(-1). This study has demonstrated that successful certification of clenbuterol-containing and clenbuterol-free bovine eye materials is possible.     

Development and certification of reference materials for residues of organochlorine and organophosphorus pesticides in beef fat ACSL CRM 1 and 2

Beef fat samples were prepared and tested as candidate reference materials for organochlorine and organophosphorus pesticides. The CRMs consisted of beef fat spiked with pesticide solutions. One sample (ACSL CRM 1) was prepared containing close to 0.2 mg/kg of each of the organochlorine pesticides dieldrin and heptachlor epoxide. A second sample (ACSL CRM 2) was prepared containing close to 0.8 mg/kg of each of the organophosphorus pesticides diazinon, chlorpyrifos and ethion. The spiking levels and homogeneity of the materials were verified. The coefficients of variation of 5 analyses carried out to test between-jar homogeneity for each reference material were dieldrin, 3.5%; heptachlor epoxide, 1.1%; diazinon, 2.1%; chlorpyrifos, 1.2% and ethion, 3.1%. No instability in any of these compounds was detected over a twelve month period. The candidate reference materials were found to be suitable for certification by interlaboratory testing. The certification process was based on a two-stage nested design described in ISO Guide 35. Analysis of results reported by collaborating laboratories provided an assessment of the homogeneity of the reference materials. The certified values together with their upper and lower 95% confidence limits are: ACSL CRM 1*Dieldrin*0.199 mg/kg **(0.188, **0.210 mg/kg) *Heptachlor epoxide*0.194 mg/kg **(0.176, **0.212 mg/kg) ACSL CRM 2*Diazinon*0.805 mg/kg **(0.755, **0.855 mg/kg) *Chlorpyrifos*0.790 mg/kg **(0.728, **0.852 mg/kg) *Ethion*0.813 mg/kg **(0.746, **0.879 mg/kg). A certificate for each material was prepared according to the guidelines set out in ISO Guide 31. Received: 25 April 1997 / Revised: 19 August 1997 / Accepted: 28 August 1997     

Development and certification of reference materials for residues of organochlorine and organophosphorus pesticides in beef fat ACSL CRM 1 and 2

Beef fat samples were prepared and tested as candidate reference materials for organochlorine and organophosphorus pesticides. The CRMs consisted of beef fat spiked with pesticide solutions. One sample (ACSL CRM 1) was prepared containing close to 0.2 mg/kg of each of the organochlorine pesticides dieldrin and heptachlor epoxide. A second sample (ACSL CRM 2) was prepared containing close to 0.8 mg/kg of each of the organophosphorus pesticides diazinon, chlorpyrifos and ethion. The spiking levels and homogeneity of the materials were verified. The coefficients of variation of 5 analyses carried out to test between-jar homogeneity for each reference material were dieldrin, 3.5%; heptachlor epoxide, 1.1%; diazinon, 2.1%; chlorpyrifos, 1.2% and ethion, 3.1%. No instability in any of these compounds was detected over a twelve month period. The candidate reference materials were found to be suitable for certification by interlaboratory testing. The certification process was based on a two-stage nested design described in ISO Guide 35. Analysis of results reported by collaborating laboratories provided an assessment of the homogeneity of the reference materials. The certified values together with their upper and lower 95% confidence limits are: ACSL CRM 1*Dieldrin*0.199 mg/kg **(0.188, **0.210 mg/kg) *Heptachlor epoxide*0.194 mg/kg **(0.176, **0.212 mg/kg) ACSL CRM 2*Diazinon*0.805 mg/kg **(0.755, **0.855 mg/kg) *Chlorpyrifos*0.790 mg/kg **(0.728, **0.852 mg/kg) *Ethion*0.813 mg/kg **(0.746, **0.879 mg/kg). A certificate for each material was prepared according to the guidelines set out in ISO Guide 31.     

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     

Use of an excess variance approach for the certification of reference materials by interlaboratory comparison

In the nuclear field, the accuracy and comparability of analytical results are crucial to insure correct accountancy, good process control and safe operational conditions. All of these require reliable measurements based on reference materials whose certified values must be obtained by robust metrological approaches according to the requirements of ISO guides 34 and 35. The data processing of the characterization step is one of the key steps of a reference material production process. Among several methods, the use of interlaboratory comparison results for reference material certification is very common. The DerSimonian and Laird excess variance approach, described and implemented in this paper, is a simple and efficient method for the data processing of interlaboratory comparison results for reference material certification. By taking into account not only the laboratory uncertainties but also the spread of the individual results into the calculation of the weighted mean, this approach minimizes the risk to get biased certified values in the case where one or several laboratories either underestimate their measurement uncertainties or do not identify all measurement biases. This statistical method has been applied to a new CETAMA plutonium reference material certified by interlaboratory comparison and has been compared to the classical weighted mean approach described in ISO Guide 35. This paper shows the benefits of using an “excess variance” approach for the certification of reference material by interlaboratory comparison.