Improvement of the traceability of reference materials certified for purity: evaluation of a semi-preparative high-performance liquid chromatography approach

A semi-preparative high-performance liquid chromatography process was evaluated as a tool to quantitatively determine the purity or percentage mass fraction content (% m/m) of organic compounds. The method is simple and does not require the identification and subsequent quantitation of organic-related structure impurities. A protocol was developed and tested on four reference materials certified for purity from 95% m/m to 99.3% m/m. Comparing the purity results of each certified reference material using the new approach with their respective certified values showed no significant analytical bias. Semi-preparative high-performance liquid chromatography has proved the potential to be a primary method directly traceable to mass with an uncertainty statement written down also in terms of mass with expanding uncertainty ranging from 0.8% to 1.3% m/m compared to 0.3 to 2.0% m/m for the certified purity values at the 95% confidence interval.     

The preparation, assay and certification of aqueous ethanol reference solutions

Internationally, certified ethanol reference materials are required to calibrate breathalysers and blood-alcohol measurement instruments. The CSIR National Metrology Laboratory of South Africa provides certified aqueous ethanol solutions with traceability to the SI. Ethanol solutions in the concentration range 10 mg/100 g to 20 g/100 g are prepared gravimetrically by mixing ethanol and reagent quality water. To verify the concentration of the ethanol it is oxidized to acetic acid with potassium dichromate in the presence of sulphuric acid. The unreacted potassium dichromate is back-titrated with sodium thiosulphate. The method utilizes gravimetry and titrimetry, which are both primary methods. This paper addresses aspects of ethanol-certified reference materials that have not been previously published: traceability, stability of unpreserved ethanol solutions, homogeneity, quality control measures and the effect of reproducibility on the measurement uncertainty. Presented at -- “BERM-10” -- April 2006, Charleston, SC, USA     

Trends in the certification of reference materials

The certification of reference materials is still a rapidly developing area. Mostly driven by demands from laboratories, new reference materials are produced, and even new categories of materials are developed, such as genetically modified organism materials or materials for qualitative analysis. Even in more classical areas, such as the certification of chemicals for purity, there are important new insights, in particular in modelling the measurements and the property values. Laboratories are asking increasingly for uncertainty budgets of reference materials that are compatible with the concepts of the Guide to the expression of uncertainty in measurement, thus putting stronger demands to improve not only the quality of the materials, but also of the science and technology behind a certification. Three important issues are highlighted to exemplify these trends: the further interpretation of homogeneity and stability data, the appreciation of asymmetry due to mathematical constraints (relevant for, e.g., purity and trace analysis), and the certification of reference materials for qualitative measurement.Presented at BERM-9—9th International Symposium on Biological and Environmental Reference Materials, 15–19June 2003, Berlin, Germany     

Matrix certified reference materials for environmental monitoring from the National Metrology Institute of Japan (NMIJ)

Matrix certified reference materials (CRMs) are playing an increasingly important role in environmental monitoring in Japan. The National Metrology Institute of Japan (NMIJ)/National Institute of Advanced Industrial Science and Technology (AIST) has been developing matrix CRMs for environmental monitoring since 2001, and has issued nine kinds of CRMs as NMIJ CRMs. The development of the CRMs was conducted in NMIJ in cooperation with candidate material producers. The isotope dilution mass spectrometry (IDMS) was principally adopted to give reliable certified values. Meanwhile, two or more analytical methods, whose levels of accuracy were well evaluated, were applied to avoid any possible analytical bias. Two typical certification processes, the certification of river water CRMs for trace element analysis and that of marine sediment CRMs for PCB and organochlorine pesticide analysis, are outlined as examples. Presented at -- “BERM-10” -- April 2006, Charleston, SC, USA.     

Development of certified reference materials of high-purity volatile organic compounds: purity assay by the freezing-point depression method

For accurate measurement of concentrations of substances by instrumental analysis, reliable calibration standards are needed. In Japan, national reference materials are supplied under the national standards dissemination system named the Japan Calibration Service System (JCSS). In JCSS, calibration standards for the analysis of environmental pollutants are supplied. For the traceability to the SI of reference materials for calibration in JCSS, the National Metrology Institute of Japan (NMIJ) is developing high-purity reference materials of volatile organic compounds (VOCs) as NMIJ CRMs. The freezing-point depression method, which has potential as a primary method of measurement, is employed for the determination of property value. In this paper, a development scheme of certified reference materials of high-purity VOCs is described. Presented at BERM-11, October 2007, Tsukuba, Japan.     

Preparation and certification of a reference material for the determination of nutrients in seawater

There is an urgent need for natural water reference materials certified for nutrients. In 1996, NRC collected seawater for a proposed CRM at a depth of 200 m in the North Atlantic; this was immediately filtered through 0.05-m cartridge filters into 50-L carboys. The water was later homogenized in the NRC laboratories in Ottawa and stabilized via gamma irradiation. Over six years of stability testing no significant deterioration was detected. In addition to the usual customary standard colorimetric procedures, alternative analytical methods were developed to enable the certification process. The production of a CRM called MOOS-1 will be discussed. Certified values, with uncertainty components addressing the homogeneity, stability, and characterization of the material, were calculated to be: orthophosphate=1.56±0.07 µmol L^–1, silicate=26.0±1.0 µmol L^–1, nitrite=3.06±0.15 µmol L^–1, and nitrite and nitrate=23.7±0.9 µmol L^–1.     

Preparation and characterization of organic calibration solutions for development of certified reference materials at the National Metrology Institute of Japan

Certified reference materials (CRMs) are playing an increasingly important role in environmental monitoring in Japan. The National Metrology Institute of Japan (NMIJ)/National Institute of Advanced Industrial Science and Technology (AIST) has been developing CRMs of organic calibration solutions since 2003, and has issued several NMIJ CRMs. The development of these materials was conducted at the NMIJ in cooperation with candidate material producers. The freezing-point depression method was principally adopted for assessment of the purity of starting materials to give reliable certified values. Gas chromatography with flame ionization detection (GC–FID) and/or high-performance liquid chromatography (HPLC), which are based on independent principles and whose levels of accuracy are well evaluated, were applied in combination with other methods to avoid any possible analytical bias. Purity assessment is outlined for two typical examples, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (p,p′-DDD) and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p′-DDT), which were used as starting materials for a CRM under development. Methods adopted for gravimetric preparation and ampouling of solutions were qualified and optimized to reduce the uncertainties of certified values due to these factors. Furthermore, a new experimental scheme for assessment of stability and preparation variation is proposed for the proper estimation of uncertainties. Presented at BERM-11, October 2007, Tsukuba, Japan.     

Improvements in efficiency of production and traceability for certification of reference materials

Issues of current interest to certified reference material producers are addressed. Alternative strategies for certification of matrix reference materials are discussed and the benefits of adopting a flexible, cost-effective approach are described. The difficulty of undertaking homogeneity testing where certification is to be carried out with definitive techniques capable of providing very small measurement uncertainty is discussed. Methodology is described which combines conventional screening of the candidate material for homogeneity with an additional, precise assessment of homogeneity based on isotope dilution mass spectrometry measurements. A systematic procedure for evaluating the commutability (horizontal traceability or scope) of matrix reference materials has been evaluated and shows that in some circumstances matrix effects may be less pervasive than is generally believed. This offers the possibility, especially for trace analysis applications, of more efficient use of existing reference materials without compromising measurement reliability. Vertical traceability of matrix reference material data is of growing interest but is difficult to achieve with present interlaboratory certification exercises. A modification is described which attempts to address this issue. It also offers the possibility of improved identification of outliers and reduced variation of data between the participating laboratories.Presented at BERM-9—9th International Symposium on Biological and Environmental Reference Materials, 15–19June 2003, Berlin, Germany     

Preparation and certification of arsenobetaine reference material NMIJ CRM 7901-a

An arsenobetaine [(CH₃)₃As⁺CH₂COO⁻] solution reference material, NMIJ CRM 7901-a, intended for use in the speciation of arsenic compounds, was developed and certified by the National Metrology Institute of Japan (NMIJ), part of the National Institute of Advanced Industrial Science and Technology (AIST). The high-purity arsenobetaine powder was synthesized from trimethylarsine [(CH₃)₃As], and it was dissolved in water in order to prepare 20 mg kg⁻¹ of arsenobetaine standard solution. The solution was bottled in 500 bottles (each containing 10 ml). Certification of the CRM for arsenobetaine was conducted by NMIJ. The concentration of As was determined by four independent analytical techniques (ICP–MS, ICP–OES, GFAAS and LC–ICP–MS), and each result was converted to the arsenobetaine concentration by applying an appropriate factor. The arsenobetaine concentration in the CRM was thus certified.     

Preparation and certification of high-grade gold geochemical reference material

One high-grade gold geochemical reference material-BND 3401.01 has been prepared by the National Geophysical Research Institute (NGRI), Hyderabad in collaboration with the Hutti Gold Mines Company Limited (HGML), Hutti and National Physical Laboratory (NPL), New Delhi, in India. The sample is a sheared gold-sulphide-bearing quartz vein emplaced in a sheared acid volcanic rock that was collected at the 2400-foot level from the middle reef of Hutti deposit located in the north-western periphery of the late-Archaean Hutti-Maski greenstone belt, Karnataka, India. Fifteen institutions in India, Canada, China and Tanzania having experience in geochemical analysis had participated in this collaborative analysis programme. The sample was extensively characterized for its major, minor, trace and ultra-trace element composition by using a variety of analytical techniques. Usable values were provided for major, minor and several trace elements including all rare earth elements (REE). The certified value for the gold concentration in BND 3401.01 gold ore is 12.1±0.7 mg/kg.     

Preparation and certification of two freshwater sediments certified reference materials for polycyclic aromatic hydrocarbons

Two freshwater sediments certified reference materials (CRMs) for 16 polycyclic aromatic hydrocarbons (PAHs) have been developed by the Institute for Environmental Reference Materials (IERM) of Ministry of Environmental Protection (MEP) in China. The methodology for preparing the CRMs of PAHs in sediments is described in this paper. The collected natural sediment samples were air-dried, ground, homogenised, packed, sterilised and tested on stability and homogeneity. Homogeneity results showed that the between-unit variation was confirmed to be below 4.5% for each compound. Stability was assessed after storage of samples for 16 months at temperature less than 30°C and in shade. The certification of the natural sediment matrix CRMs for PAHs was based on the agreement of results using different analytical techniques including gas chromatography/mass spectrometry (GC/MS) and reversed-phase liquid chromatography (LC) by no less than eight collaborating laboratories including IERM. Results of the homogeneity showed that the calculated u_bb′ was 0.9–2.5% for environmental river standard-4 (ERS-4) and 9–2.3% for environmental lake standard-1 (ELS-1), whereas stability results of total 16 PAHs indicated that the calculated u_rel,lts was 4.2% for ERS-4 and 2.2% for ELS-1. Certified values of 16 PAHs in ERS-4 varied from 8.5 to 167 μg/kg and ranged from 0.036 to 2.8 mg/kg in ELS-1.The good comparability, together with the independent confirmation of the assigned mass fraction by using different methods, confirmed that the CRMs are suitable for the method validation and quality control in soil or sediments analysis.     

The present situation of Japanese certified reference materials registered in the COMAR database

 In the field of reference materials, COMAR (Code d'Indexation des Matériaux de Référence) is now internationally known as a reliable directory. In order to improve the quality of COMAR, a document which covers general requirements for the registration of reference material has recently been adopted by the Japanese coding centre, NITE. This paper describes the general requirements for reference materials and the current status of the COMAR database coded by the National Institute of Technology and Evaluation (NITE), Japan. The concept of the requirements is fundamentally based on the ISO Guides 30, 31, 33, 34 and 35. Certifications of reference materials are divided into the following three categories in the newly adopted document. 1. Certifications based on the results of interlaboratory comparisons 2. Certifications in accordance with the Measurement Law 3. Certifications in accordance with the measurement results of national institutions An example of an uncertainty evaluation is also presented in the paper. Received: 14 October 1996 Accepted: 3 December 1996     

Development of a candidate certified reference material of cypermethrin in green tea

This paper presents the preparation of a candidate certified reference material (CRM) of cypermethrin in green tea, GLHK-11-01a according to the requirements of ISO Guide 34 and 35. Certification of the material was performed using a newly developed isotope dilution mass spectrometry (IDMS) approach, with gas chromatography high resolution mass spectrometry (GC–HRMS) and gas chromatography–tandem mass spectrometry (GC–MS/MS). Statistical analysis (one-way ANOVA) showed excellent agreement of the analytical data sets generated from the two mass spectrometric detections. The characterization methods have also been satisfactorily applied in an Asia-Pacific Metrology Program (APMP) interlaboratory comparison study. Both the GC–HRIDMS and GC–IDMS/MS methods proved to be sufficiently reliable and accurate for certification purpose. The certified value of cypermethrin in dry mass fraction was 148 μg kg⁻¹ and the associated expanded uncertainty was 14 μg kg⁻¹. The uncertainty budget was evaluated from sample in homogeneity, long-term and short-term stability and variability in the characterization procedure. GLHK-11-01a is primarily developed to support the local and wider testing community on need basis in quality assurance work and in seeking accreditation.     

The interpretation and use of stability data in the certification of reference materials

 Stability tests are carried out on candidate reference materials in order to ascertain that the certification values continue to be valid a reasonable time after completion of the certification analysis. These tests are also used for recommending storage conditions, as well as the duration of storage before certification values need be rechecked. BCR (Community Bureau of Reference) reference materials do not normally have an expiry date, but rely on stability monitoring throughout the lifetime of the certified material. The 1997 version of the BCR Guidelines for the production and certification of reference materials does, however, take into account the necessity of limiting the validity of a certification, when degradation of the material during storage cannot be ignored. This paper discusses an example of significant degradation taking place between the time of completion of the certification analysis and the issue of a formal certificate. Various options are presented together with an account of their influence on the certified values and their uncertainties. Received: 3 October 1997 · Accepted: 3 November 1997     

Scheme and studies of reference materials for volumetric analysis in Japan

This paper describes the history and scheme of reference materials and standard solutions for titrimetry in Japan. Titrimetry is one of the most fundamental and precise methods for determination of a constituent, based on the effective purity of reference materials in stoichiometric analysis. It has wide-ranging applications based on titrimetric reactions such as neutralization, redox, chelatometric, and precipitation titration processes, which are used in various analytical fields all over the world. Japanese Industrial Standards (JIS) have played an important role in establishing a stable supply of reference materials for titrimetry since the 1950s. There are several reports of preparations and their determination, including coulometric studies, in order to establish highly reliable reference materials. This paper briefly reviews the schemes and studies of standardization through the provision of reference materials and standard solutions based on JIS, and several applications in other standards. Presented at Berm-11, October 2007, Tsukuba, Japan.     

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.     

Development of a certified reference material for the content of nitroimidazole parent drugs and hydroxy metabolites in pork meat

Nitroimidazoles have been applied in the past to poultry and pigs to treat protozoan diseases and to combat bacterial infections, but due to adverse health effects their use in food-producing animals has meanwhile been banned in the EU. The request for a certified reference material in a representative matrix was stipulated by the responsible Community Reference Laboratory and is underpinned by the need to improve the accuracy and comparability of measurement data and to establish metrological traceability of analytical results. The Institute for Reference Materials and Measurements (IRMM) has responded to this demand by developing and producing a new certified matrix reference material, ERM-BB124. This incurred lyophilised pork meat material was certified according to ISO guides 34 and 35 for the mass fractions of six nitroimidazole compounds. Processing of the frozen muscle tissue to the final material was accomplished by application of cutting, freeze-drying, mixing and milling techniques. Homogeneity and stability measurements were performed using liquid chromatography tandem mass spectrometry. The relative standard uncertainty due to possible heterogeneity showed to be below 1.8% for all analytes. Potential degradation during transport and storage was assessed by isochronous stability studies. No significant instability was detected at a storage temperature of −20 °C for a shelf-life of 2 years. The certified mass fraction values were assigned upon evaluation of the data acquired in an international laboratory inter-comparison involving 12 expert laboratories using different sample preparation procedures, but exclusively LC-MS/MS methods. Relative standard uncertainty contributions for the characterisation (between-lab variation of mean values) were found to be between 1.6 and 4.8%. Certified values for five analytes were in the range of 0.7 to 6.2 μg kg⁻¹, with expanded relative uncertainties ranging between 7 and 14%. Dimetridazole could be certified as “<0.25 μg kg⁻¹ with a probability of 95%”. All values are traceable to the International System of Units (SI). The material is intended to be used for method validation purposes (including trueness estimation) and for method performance assessment.     

Adequacy in the metrology of chemical analysis and other complicated measurements

The adequacy of specimens to each other, and of reference material to routine specimens, is an important idea in the metrology of chemical analysis. However, the literature gives no strict definition for this notion. In this paper, a determination of adequacy based on the measure of adequacy is proposed. For the case of two specimens, the measure of adequacy is the absolute value of the difference between the systematic errors in the results from analysis of the specimens; it depends on the differences in the composition and properties of the specimens. The measure of adequacy of a certified reference material to a population of routine specimens is the maximum distance between the systematic error of the reference material and one of the quantiles of the systematic error distribution of the routine specimens Q(0.025); Q(0.975); the errors in this case are due to the composition and the properties of the routine specimens and other complicated measurements. When the measure of adequacy can be neglected compared to the permissible error of the analysis, the specimens are considered adequate. Using the determination of total cholesterol in the blood serum of human beings as an example, it was shown that the certified reference material used in the analysis of specimens of complex composition is often inadequate when compared to routine specimens.

Certification of methylmercury content in two fresh-frozen reference materials: SRM 1947 Lake Michigan fish tissue and SRM 1974b organics in mussel tissue (Mytilus edulis)

This paper describes the development of two independent analytical methods for the extraction and quantification of methylmercury from marine biota. The procedures involve microwave extraction, followed by derivatization and either headspace solid-phase microextraction (SPME) with a polydimethylsiloxane (PDMS)-coated silica fiber or back-extraction into iso-octane. The identification and quantification of the extracted compounds is carried out by capillary gas chromatography/mass spectrometric (GC/MS) and inductively coupled plasma mass spectrometric (GC/ICP-MS) detection. Both methods were validated for the determination of methylmercury (MeHg) concentrations in a variety of biological standard reference materials (SRMs) including fresh-frozen tissue homogenates of SRM 1946 Lake Superior fish tissue and SRM 1974a organics in mussel tissue (Mytilus edulis) and then applied to the certification effort of SRM 1947 Lake Michigan fish tissue and SRM 1974b organics in mussel tissue (Mytilus edulis). While past certifications of methylmercury in tissue SRMs have been based on two independent methods from the National Institute of Standards and Technology (NIST) and participating laboratories, the methods described within provide improved protocols and will allow future certification efforts to be based on at least two independent analytical methods within NIST.     

A re-examination of platinum-group element concentrations in the environmental certified reference material BCR-723

A detailed statistical examination of replicated data used to certify platinum-group elements (PGEs) in environmental reference material BCR-723 is presented. Certification of Pt, Pd, and Rh concentrations in BCR-723 was based on 16, eight, and nine accepted data sets, respectively. Each accepted data set contained six replicated measurements for each PGE, and the statistical properties of these concentration data were examined, i.e. 96 for Pt, 48 for Pd, and 54 for Rh. This level of investigation has received limited attention but is critical in furthering our understanding of PGE variability and representativeness. Concentrations of Pt, Pd, and Rh were shown to differ significantly between accepted data sets. Palladium and Pt differed in their quantification between detection techniques. Additionally, Pd and Pt concentrations varied significantly between laboratories using a similar definitive method (inductively coupled plasma-isotope dilution mass spectrometry). The distribution of Pd concentrations was found to be bimodal, with a secondary population exhibiting a contamination signal of about 15%. The secondary population, not previously reported in BCR-723, is likely a measurement artifact and not due to a nugget effect. Comparisons of BCR-723 with other environmental media from Europe, i.e. airborne particulate matter, tunnel dust, and road-deposited sediment, indicated that Pd is uncommonly low in BCR-723 (6.0?ng?g^?1) and is generally not representative in terms of its distribution relative to Pt and Rh. Serious consideration should be given to developing a new PGE certified environmental reference material.