Assessment of commutability for candidate certified reference material ERM-BB130 “chloramphenicol in pork”

Chloramphenicol (CAP), an effective antibiotic against many microorganisms, is meanwhile banned in the EU for treatment of food-producing animals due to adverse health effects. The Institute for Reference Materials and Measurements (IRMM) is currently developing a certified reference material (CRM) for CAP in pork, intended for validation and method performance verifications of analytical methods. The material will be certified using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatography–mass spectrometry (GC–MS) methods and has a target CAP level around the minimum required performance limit (MRPL) of 0.3 μg/kg. To prove that the material can be applied as a quality control tool for screening methods, a commutability study was conducted, involving five commercially available enzyme-linked immunosorbent assay kits and one biosensor assay (BiaCore kit). Meat homogenates (cryo-milled wet tissue) with CAP concentrations around the MRPL and the candidate CRM (lyophilised powder) were measured by LC–MS/MS and GC–MS as well as the six screening methods. Pairwise method comparisons of results obtained for the two sample types showed that the CRM can successfully be applied as quality control (QC) sample to all six screening methods. The study suggests that ERM-BB130 is sufficiently commutable with the investigated assays and that laboratories applying one of the investigated kits therefore benefit from using ERM-BB130 to demonstrate the correctness of their results. However, differences among the assays were observed, either in the abundance of bias between screening and confirmatory LC and GC methods, the repeatability of test results, or goodness of fit between the methods.     

Interlaboratory comparisons – demonstrating degree of equivalence

 The role of matrix reference materials in the process of demonstrating the degree of equivalence of measurement results obtained from intercomparisons is outlined, reviewing exemplary selected experience gained at BAM regarding the determination of organic contaminants in environmental matrices. The specific characteristics of reference materials employed in the process of demonstrating equivalence between laboratories in the course of proficiency testing as well as the development, comparison and validation of methods are elaborated. The demand is for series of appropriately characterised samples which are fit for the purpose and it is seen from representative examples that the utilisation of such tailor-made RM designed to tackle the specific need of an analytical problem dominates over certified matrix reference materials in this context. Concluding, the role of certified matrix reference materials in quality assurance is briefly looked at both from the user’s and providers’ points of view. Received: 9 September 2002 Accepted: 16 December 2002 Presented at CERMM-3, Central European Reference Materials and Measurements Conference: The function of reference materials in the measurement process, May 30–June 1, 2002, Rogaška Slatina, Slovenia Correspondence to R. Becker     

Measurement of progesterone in human serum by isotope dilution liquid chromatography–tandem mass spectrometry and comparison with the commercial chemiluminescence immunoassay

Progesterone is one of the steroid hormones. The hormone is especially important in preparing the uterus for the implantation of the blastocyst and in maintaining pregnancy. Its concentration in serum is measured to determine ovarian function and to predict early pregnancy. The progesterone concentration is also important for in-vitro fertilization and embryo-transfer outcomes. We have established isotope dilution liquid chromatography–tandem mass spectrometry as a primary method for the measurement of progesterone in human serum. Progesterone and its isotopic analogue, progesterone-¹³C₂, in serum were monitored at mass transitions of m/z 315.2/109.2 and 317.2/111.2 respectively in multiple-reaction monitoring (MRM) mode with electrospray positive ionization. For validation of the method, progesterone in a National Institute of Standards and Technology standard reference material (NIST SRM) was measured, and the measured results were in good agreement with the reference values within the uncertainty. On the basis of the established method, progesterone certified reference material (CRM) was developed in this work. The certified value was (1.41 ± 0.036) μg kg⁻¹. The repeatability of 1.1% and reproducibility of 0.14% showed that ID LC–MS–MS is a reliable and reproducible method. The expanded uncertainty for the measurement of progesterone in the CRM was approximately 2.6% within 95% confidence limits. The detection limit of progesterone was approximately 0.6 μg kg⁻¹. The progesterone CRMs were distributed to representative clinical laboratories in the Republic of Korea for comparison with the chemiluminescence immunoassay (CLIA), which is the most sensitive immunoassay method. The results from the comparison showed quite a large bias among the participating laboratories. This implies that the CRM is a very important material for establishment of traceability to its practical use.     

Determination of POPs in environmental matrices – proficiency tests for Polish laboratories

Thirty Polish laboratories participated in proficiency tests (PT) for determination of persistent organic pollutants – POPs (PCBs – polychlorinated biphenyls, PAHs – polyaromatic hydrocarbons and pesticides) in solid environmental matrices (sediments, soil). Participants used their in-house method. The aim of the exercises was to obtain information about the “state of the art” of POPs analysis in environmental samples. The CV (coefficient of variation) of analytical results submitted varied from 45 to 65%, with an outlier rate 2 to 7%. The averages of results for all analytes were in good agreement with reference values. Statistical treatment of results was made. Comparison of the each result with the certified values characterizing the material has been done. Additionally, z-scores were calculated taking into account the uncertainty of a certified value and the acceptable deviation from the certified value in the range of −20% to +10% (in accordance with recommendations in the newest directives of European Union (EU) [1]); For rejecting outliers Hampel test has been applied.     

A DANREF certified reference plastic for measurement of overall migration into the food simulant olive oil by single sided testing

A reference material for the determination of overall migration from a plastic coextrudate into the fatty food simulant olive oil was produced and certified in an interlaboratory study. The analyses were carried out according to the ENV 1186 standard from the European Committee for Standardization (CEN) [1, 2, 3] with exposure of the coextrudate to olive oil for 10 days at 40?°C. After an initial preliminary interlaboratory study eight laboratories participated in the certification round, and two different methods were used to obtain single sided exposure of the plastic to the oil. The certified value was determined as the mean of laboratory mean values. No outliers were found. A reference value of 8.6 mg/dm²± 1.4 mg/dm² (± half width of the 95% confidence interval) was obtained which is within the range relevant for the regulatory limit (10 mg/ dm²), making this reference material suitable for laboratories measuring according to the EU overall migration limit [4]. The material has been found stable over 45 months.     

A DANREF certified reference plastic for measurement of overall migration into the food simulant olive oil by single sided testing

A reference material for the determination of overall migration from a plastic coextrudate into the fatty food simulant olive oil was produced and certified in an interlaboratory study. The analyses were carried out according to the ENV 1186 standard from the European Committee for Standardization (CEN) [ 1, 2, 3] with exposure of the coextrudate to olive oil for 10 days at 40 degrees C. After an initial preliminary interlaboratory study eight laboratories participated in the certification round, and two different methods were used to obtain single sided exposure of the plastic to the oil. The certified value was determined as the mean of laboratory mean values. No outliers were found. A reference value of 8.6 mg/dm2 +/- 1.4 mg/dm2 (+/- half width of the 95% confidence interval) was obtained which is within the range relevant for the regulatory limit (10 mg/ dm2), making this reference material suitable for laboratories measuring according to the EU overall migration limit [4]. The material has been found stable over 45 months.     

Key metrological issues in proficiency testing––response to “Metrological compatibility-a key issue in further accreditation” by K. Heydorn

A discussion of proficiency testing (PT) topics started by Heydorn (Accred Qual Assur 15:643–645, 2010) is continued in the present paper. The role of PT in the accreditation of testing/analytical laboratories, the use of consensus values (average or weighted average, median, observed standard deviation, etc.) and a metrological background of PT schemes are discussed. It is shown that metrological traceability, comparability, and compatibility, as well as commutability of a reference material, are the key issues of any PT scheme that applies certified reference material as test items. Metrological compatibility of PT results in such schemes is a property demonstrating the closeness of the PT results to the certified value in comparison with the measurement uncertainty of their difference. The metrological background is especially important for the selection and use of PT schemes for a limited number of participants (fewer than 30) as detailed in IUPAC/CITAC Guide on the topic published in 2010 in Pure Appl Chem 82(5):1099–1135.     

Analysis of a copper alloy: Comité Consultatif pour la Quantite de Matière (CCQM) pilot study P76 international intercomparison

The capabilities of National Metrology Institutes (NMIs) and selected outside “expert” laboratories of determining the mass fractions of the main and minor elements Cu, Pb, Sn, Fe, and Ni in a lead-containing brass were assessed. This pilot study P76 was organized as an activity of the Inorganic Analysis Working Group of CCQM and was piloted by the Federal Institute for Materials Research and Testing (BAM). In total 12 laboratories (four NMIs and eight outside labs) submitted results, some of them more than one set of results per element. The laboratories were free to choose any analytical method they wanted to use for the analysis. Consequently various methods of measurement were employed: inductively coupled plasma optical emission spectrometry (ICP–OES), inductively coupled plasma mass spectrometry (ICP–MS), instrumental neutron-activation analysis (INAA), titrimetry, flame atomic-absorption spectrometry (FAAS), spectrophotometry (MAS), electrogravimetry, and gravimetric analysis. After testing for homogeneity within BAM, a certified reference material of lead-containing brass was used as test sample without informing the participants about the source of the material. The agreement of the results for all elements investigated was acceptable and mean values calculated from the results of all participants were close to the certified mass fractions of the CRM used as test sample. No statistically significant differences between the results of the NMIs and those of the non-NMIs could be observed.     

Development and certification of the new NIES CRM 28: urban aerosols for the determination of multielements

A new environmental certified reference material (CRM) for the determination of multielements in aerosol particulate matter has been developed and certified by the National Institute for Environmental Studies (NIES), Japan, based on analyses by a network of laboratories using a wide range of methods. The origin of the material was atmospheric particulate matter collected on filters in a central ventilating system in a building in Beijing city centre. The homogeneity and stability of this material were sufficient for its use as a reference material. Values for elemental mass fractions in the material were statistically determined based on the analytical results of the participating laboratories. Eighteen certified values and 14 reference values were obtained. The diameters, obtained from a micrographic image using image analysis software, of 99% of the particles were less than 10 μm, demonstrating that almost all the particles in the material could be classified as particles of 10 μm or less in aerodynamic diameter. The chemical composition and particle size distribution of this material were close to those of an authentic aerosol collected in Beijing. NIES CRM 28 is appropriate for use in analytical quality control and in the evaluation of methods used in the analysis of aerosols, particularly those collected in urban environments in northeast Asia Figure New NIES CRM 28 Urban Aerosols and photo micrograph of the material     

An international assessment of the metrological equivalence of higher-order measurement services for creatinine in serum

The Consultative committee for amount of substance-metrology in chemistry (CCQM)-K80 Key Comparison directly assessed the equivalence of many of the world’s higher-order value-assigned materials (HOVAMs) for creatinine in human serum. This 2009 international study compared the certified values and uncertainties of the materials using measurements made under repeatability conditions. The study evaluated 17 materials submitted by 6 national metrology institutes (NMIs). The creatinine quantity in these materials ranged from 3 mg/kg to 57 mg/kg (about 0.3 mg/dL to 6 mg/dL or 30 nmol/L to 500 nmol/L). All materials were stored and prepared according the specifications provided by the participating NMIs. Samples were processed and analyzed under repeatability conditions by one analyst using isotope-dilution liquid chromatography–mass spectrometry in two measurement campaigns. The certified values and repeatability measurements were compared using uncertainty-weighted generalized distance regression. The instrumental repeatability relative standard deviation was 1.2%. The measurement design required assessment of within-unit and between-campaign variability in addition to measurement repeatability. At a 95% level of confidence, the certified values for all 17 materials agreed to within their assigned uncertainties. CCQM-K80 demonstrated the metrological equivalence of the currently available HOVAMs for creatinine in human serum and of the creatinine measurement services provided by the participating NMIs.     

Determination of niacin in infant formula by solid-phase extraction/liquid chromatography: peer-verified method performance-interlaboratory validation

This paper reports the results of the interlaboratory peer validation study of AOAC Peer-Verified Method (PVM) 1:2,000 for the determination of niacin in infant formula by solid-phase extraction/liquid chromatography. We have used a Data Quality Objectives (DQO) approach to address not only method variability and robustness but also accuracy of data through the use of an appropriate reference material in conjunction with the interlaboratory validation study. Our DQO included the following: (1) statistical agreement of analytical results and quantitative recovery between 2 collaborating laboratories; (2) the repeatability relative standard deviation (RSDr) values and the HORRAT (Horwitz ratio) obtained (1.07), which satisfied the criteria of the Horwitz "limits of acceptability" at the analyte level present; (3) validation of lack of interference; and (4) accuracy agreement within assigned values for a certified reference material. National Institute of Standards and Technology Standard Reference Material (NIST SRM) 1846 Infant Formula, with a certified value of 63.3 +/- 7.6 microg/g for niacin content, was used as a test material for collaborative study and accuracy assessment. Niacin values obtained by the originating laboratory were 59.7 +/- 4.0 microg/g (95% confidence interval [CI] = 1.4 microg/g with a relative standard deviation [RSD] of 6.7%) and by the peer laboratory were 56.6 +/- 6.6 microg/g (95% CI = 4.1 microg/g, with an RSD of 11.7%). Statistical evaluation using the means equivalence test showed that nicotinic acid values obtained by the peer laboratory were equivalent to those values obtained by the originating laboratory. Linear calibration curves and quantitative recovery were obtained. Integration of the PVM process with a readily available certified reference material gives the user confidence in the accuracy of the data generated by the method through traceability to the reference material used.     

Copper determination after FI on-line sorbent preconcentration using 1-nitroso-2-naphthol as a complexing reagent

The suitability of 1-nitroso-2-naphthol as a complexing agent for on-line preconcentration of copper using RP-C₁₈ material in a microcolumn with flow injection coupled with flame atomic absorption spectrometry (FI-FAAS) has been tested. Various parameters affecting complex formation, such as pH, sample flow rate, etc. and its elution into the nebulizer of FAAS were optimized. ?A 5 × 10^–3 mol/L reagent was on-line mixed with aqueous sample solution acidified with 0.1% (v/v) nitric acid ?(pH 3–4) and flowed through the microcolumn for 30 s. The adsorbed complexes in the microcolumn were eluted with ethanol in 10 s into the nebulizer of FAAS. A good precision (1.7% for 50 μg/L copper, n = 12), high enrichment factor (19) with detection limit (3σ) 2.0 μg/L, and sample throughput (90 h^–1) were obtained. The method was applied to certified reference materials seawater, mussel (biological), NBS-362 and NBS-364 (special low alloy steel), for the determination of copper, and the results were in good agreement with the certified values. Received: 4 May 1999 / Revised: 25 June 1999 / Accepted: 29 June 1999     

Interlaboratory comparison for the determination of pesticide residues in Chinese cabbage

The results of and findings from an interlaboratory comparison among laboratories carrying out food testing of pesticide residues in the APEC (Asia–Pacific Economic Cooperation) region are presented and discussed to show critical roles of chemical metrology infrastructure in establishing traceability of measurements and in supporting existing measurement capability in safety and quality of food trade. The study material, which was prepared and certified by Korea Research Institute of Standards and Science (KRISS), was freeze-dried Chinese cabbage powder fortified with two organophosphorous pesticides (diazinon and chlorpyrifos). Among 14 participants, 12 laboratories were accredited based on ISO/IEC17025 and one laboratory was under assessment for the accreditation at the time of this study. Though all participants demonstrated very good intra-day repeatability and inter-day intermediate precision, many of them showed a large bias from the certified values. It is suggested that in addition to the accreditation system, economies are encouraged to develop appropriate chemical metrology infrastructure, which could effectively support laboratories to assure measurement traceability to SI, for which NMIs could play significant roles through their metrological services recognized in Mutual Recognition Arrangement (MRA) of the International Committee for Weights and Measures (Comité International des Poids et Mesures, CIPM).     

Mineral oil content in sediments and soils: comparability, traceability and a certified reference material for quality assurance

The performance of twelve laboratories with previously established proficiency in the determination of the mineral oil content in a fresh water sediment is described. The summation parameter total petrol hydrocarbon (TPH) is defined according to ISO 16703:2004 with regard to the sample preparation to be applied, the flame ionisation detection (FID) and the boiling range of C₁₀–C₄₀ to be integrated. Comprehensive tests of homogeneity and stability have been carried out on the candidate material using appropriate models. The outcome of the study served as the basis for the certification of the candidate reference material as ERM-CC015a. The certified mass fraction is 1,820±130mgkg⁻¹and traceability was established by using an appropriate calibration standard certified for the mass fraction of C₁₀–C₄₀. The interlaboratory scatter of measurement results in this exercise can largely be explained by the variability of the individual calibrations based on this common calibration standard.     

Results and effects of homogeneity and stability studies carried out by X-ray fluorescence on the new reference material BAM-H010

The Federal Institute for materials research and testing (BAM) in cooperation with the Fachhochschule Münster has developed a new certified polymeric reference material, BAM-H010. The reference material consists of acrylonitrile–butadiene–styrene terpolymer (ABS) and has been doped with different contents of the elements Br, Cd, Cr, Hg and Pb. The monitoring of these elements is demanded in the EU directive 2002/95/EG, commonly referred to as RoHS. We have shown that the uncertainty contribution of the thermal long-term stability (u _stability) is negligible compared to the contribution to the uncertainty caused by the method used for the characterization of the elemental content and the batch inhomogeneity (u _homogeneity). The stability of the ABS material during exposure of the samples with hard X-radiation leads to a degradation of the ABS matrix with either long- or short-chain products.     

Determination of polybrominated diphenyl ethers in indoor dust standard reference materials

Polybrominated diphenyl ethers (PBDEs) have been measured for the first time in three different indoor dust Standard Reference Materials (SRMs) prepared by the National Institute of Standards and Technology (NIST). Two of these, SRM 2583 (Trace Elements in Indoor Dust) and SRM 2584 (Trace Elements in Indoor Dust), have been certified previously for lead and other inorganic constituents. A third, SRM 2585 (Organics in Indoor Dust), is a new indoor dust reference material prepared by NIST which will be certified for various organic compounds (polycyclic aromatic hydrocarbons, pesticides and polychlorinated biphenyls) in 2005 including certified concentrations for 16 individual PBDE congeners and reference values for an additional three PBDE congeners. Dust SRMs were analyzed for 30 PBDE congeners using high-resolution gas chromatography combined with low-resolution mass spectrometry operated in both negative chemical ionization (GC/ECNI–MS) and electron impact ionization (GC/EI–MS) modes. Sensitivity was an order of magnitude higher using GC/ECNI–MS relative to GC/EI–MS. These SRMs have been characterized and compared to the three PBDE commercial products (pentaBDE, octaBDE and decaBDE). PentaBDE and DecaBDE were present in all three SRMs and were the dominant commercial products, making up approximately 33% and 58%, respectively. Recent studies suggest that house dust may be a leading source of human exposure to PBDEs. These SRMs are the first reference materials with certified concentrations for PBDEs, which will aid in validating future measurements of PBDEs in house dust and other similar matrices. Electronic Supplementary Material Supplementary material is available for this article at http://dx.doi.org/ 10.1007/s00216-005-0227-y     

Preliminary study to prepare a reference material of styrene metabolites – mandelic acid and phenylglyoxylic acid – in human urine

 A preliminary batch of the reference material was prepared by freeze-drying pooled urine samples obtained from healthy persons occupationally exposed to styrene. Tests for homogeneity and stability were performed by determining urine concentrations of mandelic (MA) and phenylglyoxylic acids (PGA). The urinary MA and PGA concentrations were followed over an 8-month period using high performance liquid chromatography (HPLC). No changes of the concentration values were found. Pure PA and PGA from Merck and Fluka, respectively, were used for traceability purposes, because certified or standard reference materials for MA and PGA do not exist. Control material ClinChek-Urine Control (Recipe) was analysed simultaneously. The mean values of MA and PGA compared well with the means of control samples and fell within the control range. The certified values and their uncertainties were evaluated from the results of interlaboratory comparisons, homogeneity (277.0 ± 7.4 mg L⁻¹ for MA and 148.0 ± 4.7 mg L⁻¹ for FGA) and stability tests. The values are unweighted arithmetical averages of accepted results and their uncertainties are combined uncertainties enlarged by coefficient k=1, evaluated from the standard uncertainties of the interlaboratory comparison, homogeneity and stability tests. Received: 17 September 2002 Accepted: 1 November 2002 Acknowledgement This work was supported by the Internal Grant Agency of Ministry of Health of the Czech Republic (Grant NJ/6784–3). Presented at CERMM-3, Central European Reference Materials and Measurements Conference: The function of reference materials in the measurement process, May 30–June 1, 2002, Rogaška Slatina, Slovenia Correspondence to I. Šperlingová     

Statistical analysis of serum protein electrophoresis results in External Quality Assessment schemes

The goal of External Quality Assessment (EQA) schemes is to ensure that results obtained on a particular specimen in a given clinical laboratory are compatible with those obtained by other laboratories on the same specimen. Serum protein electrophoresis is a laboratory test consisting of five fractions (albumin, α₁, α₂, β and γ globulins), which sum up to 100% of total proteins. So far, in EQA schemes the five fractions have been analyzed separately as for ordinary tests like glucose or cholesterol. This approach does not consider the fractions as a whole and the linear relationship between them. A statistical approach has been developed to analyze EQA electrophoresis results from a global standpoint by using robust multivariate method to eliminate the effect of outlying profiles. As illustrated on electrophoretic data from the Belgian EQA scheme, the novel approach improves the detection of poor performing laboratories. The method will be implemented in the Belgian EQA scheme on a routine basis.     

Uncertainties of mercury determinations in biological materials using an atomic absorption spectrometer – AMA 254

 The method is based on catalysed ignition of a sample portion in a flow of oxygen, capture of mercury by an amalgamator and measurement of the mercury vapour's absorbance after thermic release from the amalgamator. Three powdered food samples, a certified reference material (CRM) human hair and a reference material (RM) urine (liquid) were measured in the first range of the instrument (the possible contents determined according to our measurement procedure were 0.0003–0.5 ppm). The calibration function used was a line passing through the origin. The combined standard uncertainties of the mercury determinations were computed from uncertainty components of five quantities: absorbance of the sample, absorbance of the sample blank, slope of the calibration line, correction factor of the abscissa axis, and mass or volume of the sample. The most important uncertainty component is the uncertainty of the sample absorbance measurement which amounts to 52% of the determination uncertainty at the minimum (RM urine) and about 90% at the maximum (in our laboratory homogenized powdered food samples; analysis of variance showed their homogeneity to be insufficient). The results of the CRM and RM analyses do not indicate a significant systematic error for this determination. The relative expanded uncertainty (coefficient was 2) of the determination increases from 9 to 13% for the insufficiently homogenized samples with decreasing mercury content (range of 0.004–0.03 ppm); higher homogeneity of samples results in a decrease of the expanded uncertainty, e.g. 4.6% for the liquid sample (RM urine). Received: 26 April 1999 / Accepted: 30 August 1999     

Quality assurance in analytical laboratories engaged in research and development activities

 Research and development activities are carried out by various types of laboratories that are not the typical testing and calibration laboratories for which the ISO/IEC 17025 is the quality assurance implementation reference. In this paper, such laboratories engaged in R&D activities are classified and different approaches they can adopt with a view to implementing a quality system that are suited to their characteristics and the type of work they conduct are proposed. These approaches take account of existing standards for the certification/accreditation of laboratories and of guides on quality assurance for non-routine analytical laboratories. Received: 11 July 2002 Accepted: 29 November 2002 Presented at Analytica Conference, 23–26 April 2002, Munich, Germany Correspondence to M. Valcárcel