Production Of Reference Materials Research Articles

Certified reference material for coal in accordance with the PN-EN ISO 17034:2017-03 standard and ISO GUIDE 35:2017

Abstract Due to an absence of domestic certified reference materials for coal on the Polish market, an attempt was made to manufacture a new and innovative product tailored to its needs. The chosen candidate material was hard coal acquired from Poland’s coal mines. A single reference material unit consisted of 50g of an analytical hard coal sample with a grain size below 0.2 mm. A manufacturing method was developed enabling production of matrix reference materials addressing the needs of the domestic solid fuel market, and was directed at research laboratories carrying out analyses of solid fuels for the energy and coking sectors. The adapted manufacturing scheme of a certified reference material for coal was presented with a description of the chosen critical steps of the process and discussion of the obtained results in terms of homogeneity, stability, characterisation of the reference material as well as assigned values to particular properties and their uncertainty budget. The results obtained during homogeneity, short-term and long-term stability assessments as well as reference material characterisation confirmed the feasibility of the investigated certified coal reference material manufacturing process. The obtained levels of relative expanded uncertainties of the measurements confirmed the feasibility of the manufactured certified reference material for establishing and maintaining metrological traceability of measurement results. The presented research establishes a base for planning out production of additional reference materials as well as providing the know-how for designing manufacturing schemes for reference materials for solid fuels, or waste related materials like fly ash, or furnace waste.

The production of polymer reference materials for microanalysis with high homogeneity by a 3D printing method

Creative use of 3D printing to create analytical standards greatly increased the sample homogeneity and the accuracy of the desired concentration.

Assay of sodium carbonate

Main textThe CCQM-K173 Assay of Sodium Carbonate key comparison was jointly organized by the Inorganic Analysis (IAWG) and Electrochemical Analysis and Classical Chemical Methods (EAWG) working groups of CCQM to test the abilities of the national metrology institutes (NMIs) to measure the purity or amount content of solid bases. They are important challenges for reference material producers, providers of other measurement services, such as proficiency testing schemes. Evidence of successful participation in formal, relevant international comparisons are needed to support calibration and measurement capability claims (CMCs) made by NMIs and designated institutes (DIs).Nine NMIs participated in this key comparison CCQM-K173. National Institute of Metrology P. R. China (NIM) and Ural Research Institute for Metrology - Affiliated Branch of the D.I. Mendeleyev Institute for Metrology (VNIIM-UNIIM), Russian Federation, acted as the coordinating laboratories of the comparison.The measurement methods used by the participants for measuring the amount content of bases expressed as sodium carbonate were coulometry and titrimetry.In general, good overlap of results was observed, the suitability of coulometry and titrimetry for assay of high purity materials was demonstrated. The majority of results were split in two groups differing from each. This bias was however covered by the stated uncertainty estimates. Various effects have been evaluated that may cause it. However, the reason for the bias has not been identified clearly.To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/.The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

CCQM Key Comparison track A CCQM-K168: Non-polar analytes in high carbohydrate food matrix: trans-zearalenone in maize powder

Main textDemonstrating competency and equivalence for the measurement capacity of contaminants and nutrients in primary foodstuffs is a priority of the OAWG 10-year strategy for Track A core comparisons. Such measurements have posed significant challenges for reference material producers and calibration service providers. This key comparison (KC), under the topic of "non- polar analyte in high carbohydrate food matrix: trans-Zearalenone (trans-ZEN) in maize powder", was a sector of the model system selected to align with this class within the OAWG strategy. Evidence of successful participation in formal, relevant international comparisons is needed to demonstrate the Calibration and Measurement Capabilities (CMCs) of National Metrology Institutes (NMIs) and Designated Institutes (DIs).17 NMIs and DIs participated in the Track A KC CCQM-K168 "non-polar analyte in high carbohydrate food matrix: trans-ZEN in maize powder". Participants were requested to evaluate the mass fraction (μg/kg) of trans-ZEN in maize powder material. Methods like liquid-liquid extraction and SPE were applied in the pre-treatment, and HPLC-MS/MS and HPLC-FLD were used for detection by the participants. The mass fractions for trans-ZEN were in the range of (91.8 to 169) μg/kg with standard uncertainties of (1.5 to 24.7) μg/kg, and corresponding relative standard uncertainties from 1.5% to 14.6%. Two laboratories, INTI and BAM were excluded from the key comparison reference value (KCRV) evaluation. INTI result was identified as an outlier and confirmed their method had insufficient specificity. For BAM the calibration approach they used does not meet the CIPM traceability requirements. The other 15 laboratories included in the calculation of the consensus KCRV all agreed within their standard uncertainties. Hierarchical Bayes was used as estimators in calculating KCRV and standard uncertainty.Successful participation in CCQM-K168 demonstrates the measurement capabilities in determining mass fraction of organic compounds, with molecular mass of 100 g/mol to 500 g/mol, having low polarity pKow < -2, in mass fraction range from 1 μg/kg to 1000 μg/kg in a high carbohydrate food matrix.To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/.The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Characterization of rye flours and their potential as reference material for gluten analysis

The safety of gluten-free products relies on accurate gluten analysis, most commonly using ELISA. These test kits are calibrated to gliadins or wheat gluten, because there is no reference material (RM) for rye. Our aim was to select representative samples out of 32 rye cultivars for use as RM. All cultivars were characterized by RP-HPLC, gel permeation HPLC and R5 and G12 ELISA. The protein and gluten content ranged from 5.5 to 11.2 g/100 g and 3.0 to 7.8 g/100 g, respectively. The average protein distribution was 40% albumins/globulins, 23% γ-75k-secalins, 17% γ-40k-secalins, 14% ω-secalins and 6% high-molecular-weight-secalins. The mean prolamin/glutelin ratio was 4.4 for rye and this translates to an estimated conversion factor from rye prolamins to gluten of 1.2, instead of the usual factor of 2. Seven cultivars were selected for RM production based on cluster analysis, geographical origin and availability to comprehensively cover the diversity of rye.

PM 7/153 (1) Mechanical inoculation of test plants

PM 7/153 (1) Mechanical inoculation of test plants

Separation of thorium from uranium in support of particle reference material production

Separation of thorium from uranium in support of particle reference material production

Identification and determination of structurally related peptide impurities in thymalfasin by liquid chromatography-high-resolution mass spectrometry.

Thymalfasin is an important peptide drug widely used for the single or combination treatment of hepatitis, sepsis, cancer, and immunodeficiency. Accurate purity assessment of thymalfasin material is essential for thymalfasin certified reference materials (CRMs) production and analytical method validation, in which comprehensive determination of thymalfasin-related impurities is required to avoid quantitative bias. In this study, liquid chromatography-high-resolution mass spectrometry (LC-hrMS) methods have been established to comprehensively characterize and quantify thymalfasin-related impurities using a thymalfasin China Pharmacopoeia (ChP) standard and then successfully applied to three commercial thymalfasin materials. A total of twenty-three thymalfasin-related impurities (> 0.1mg/g) were separated, identified, and quantified in the ChP standard analyzed. The major impurities existing in thymalfasin ChP standard and commercial materials include deamination, amination, succinimide, amino acid insertion/deletion, dimers, and isomers at different mass fraction levels. In particular, over half of the thymalfasin-related impurities were found directly or indirectly arising from the labile C-terminal asparagine (Asn) residue. Given the 28th Asn residue at the C-terminus is not necessary for the biological activity of thymalfasin as reported previously, thus deletion, replacement, or modification of thymalfasin C-terminal Asn residue is proposed for new drug research and development. In summary, these results provide a further complement to the thymalfasin-related impurity profile and issue a warning for protection or processing of the thymalfasin C-terminal Asn residue.

Bottom-up uncertainty evaluation of complex measurements from correlated performance data: Determination of total Cr in yeast by ICP-MS after acid digestion

The objective interpretation of a measurement result requires knowing the associated uncertainty. The cost-effective collection of measurement performance data on the same day produces correlated values that can affect measurement uncertainty evaluation. This work describes a novel methodology for the bottom-up evaluation of measurements based on complex sample pretreatment and the instrumental quantification of the prepared sample applicable to correlated inputs. The numerical Kragten method is used to combine the uncertainty components shared in various analyte recovery determinations. The developed methodology was applied to the determination of total chromium in yeast samples by ICP-MS after microwave-assisted acid digestion. The developed analysis of yeast samples is fit for monitoring the contamination of this product since it is associated with a relative expanded uncertainty, U’, lower than 20%, ranging from 8.4% to 10.0% in determinations of Cr between 0.125 mg/kg and 305.5 mg/kg. Duplicate analyses are adequate for reference materials production (U′ < 7%).

Enhancing cell resistance for production of mixed microbiological reference materials with Salmonella and coliforms by freeze-drying.

The reference material (RM) is a technical requirement for the quality assurance of analytical results and proficiency tests or interlaboratory comparisons. Microbiological RMs are most available in the dehydrated form, mainly by freeze-drying, and maintaining bacterial survival after preparation is a challenge. Thus, obtaining the most resistant cells is essential. Considering that bacteria present cross-response to dehydration after being submitted to an array of stress conditions, this study aimed to evaluate the influence of growth conditions on enterobacteria for the production of mixed microbiological RMs by freeze-drying in skim milk powder. Salmonella enterica serovar Enteritidis, Cronobacter sakazakii, Escherichia coli, and Citrobacter freundii were grown in a minimal medium with 0.5M NaCl and 0 to 5.0mM of manganese sulfate (MnSO4) until stationary phase. Salmonella Enteritidis presented an increased resistance to dehydration in the presence of Mn, while C. sakazakii was the most resistant to freeze-drying and further storage for 90days. Mixed microbiological RMs were produced by freeze-drying and containing Salmonella Enteritidis and coliforms in skim milk powder with 100mM of trehalose and the Salmonella survival rate was 91.2 to 93.6%. The mixed RM was stable after 30days at -20°C, and Salmonella and coliforms were detected by different methods being, the Rambach Agar the best for the bacterial differentiation. The results showed that the culture conditions applied in this study resulted in bacterial cells being more resistant to dehydration, freeze-drying, and stabilization for the production of mixed microbiological RMs more stable and homogeneous.

Accelerator mass spectrometry measurements of 93Zr for astrophysical and nuclear technology applications

Zirconium-93 is a long-lived radionuclide with a half-life of (1.61 ± 0.05) × 106 yr. Production cross sections for 93Zr by neutron capture on stable 92Zr in the keV and thermal energy ranges are important input parameters for astrophysical network calculations and nuclear industry, respectively. Despite their importance, existing experimental data suffer from large uncertainties. Here, the combination of neutron activation and accelerator mass spectrometry (AMS) is presented as an alternative method to online time-of-flight measurements for the determination of these cross sections. The main challenges for AMS of 93Zr are the interference from the stable isobar 93Nb and the production of suitable reference material. At the Heavy Ion Accelerator Facility (HIAF) the first challenge is tackled with the available high particle energies and by investigating different Zr compounds and extracted molecular beams. Using ZrF5− beams extracted from ZrF4 sample material, it is shown that the Nb background can be reduced by up to two orders of magnitude relative to the extraction of ZrO− beams from ZrO2. Using the 13+ charge state and particle energies of ∼190 MeV, 93Zr/Zr background levels in the 10−12 range are regularly achieved at HIAF. The ZrF5− output from ZrF4 samples may be highly variable but can be stabilised using an intimate mixture of ZrF4 and PbF2 at a ratio of 1:10 that has been dried down from a concentrated hydrofluoric acid solution. An option to produce a well-characterised 93Zr reference material by utilising the well-known 235U-fission yield of 93Zr is discussed. Once this remaining challenge is resolved, accurate measurements of the astrophysically and technologically relevant neutron-capture cross sections of 92Zr using AMS will be possible at HIAF.

Metrological traceability of the breath alcohol measurements

Breath alcohol measurements are widely used worldwide to detect the presence of alcohol in the human body. For those measurements, different metrological traceability chains are used, both in the international normative documents and at the national level. Different measurement standards used to calibrate breath analysers reproduce different quantities: on the one hand, an «actual» ethanol mass concentration, and, on the other hand, the operationally defined «ethanol mass concentration by Dubowski (or Harger)». This makes the comparability of the breath alcohol measurements questionable. According to various studies, the discrepancy between the operationally defined quantity and the concentration not related to the empirical interphase distribution coefficients, lays within (1-2) %, although there is also an evidence of a larger deviation. It is possible to construct a common metrological traceability chain by using reference gas mixtures in cylinders and dynamic gas mixture generators based on the principles not related to empirical equations, as well as determining more accurately the interphase distribution coefficient and evaluating its uncertainty. SE «Ukrmetrteststandart» possesses internationally recognised calibration and measurement capabilities for measuring ethanol concentration and producing reference materials: calibration gas mixtures of ethanol with nitrogen or air in cylinders and reference aqueous solutions of ethanol that provide metrological traceability for the breath alcohol measurements.

Reference material for the spectral analysis of the VSDP‑16 aluminum alloy

The control of the chemical composition of aluminum-based cathodes of the VSDP brand requires a lot of production time, as well as the availability of expensive equipment, which is not suitable for the control of the alloy composition during its smelting. The purpose of this study is to develop a technology for reference material (RM) production for spectral analysis of the VSDP-16 aluminum alloy, which meets the requirements for stability and chemical homogeneity. The RM certified values should cover the alloying range of the alloy for constructing correct calibrations in the calibration of spectrometers.The RM production technology included: melting of ingots of charge bars from the VSDP-16 alloy in a vacuum induction furnace; atomization of bars to aluminum powder; hot pressing of the resulting powder in a graphite mold on a hot pressing unit at a sintering temperature of 600C and a pressure of 20 MPa (62 kN); mechanical processing of the obtained bars. In the course of the study, the processing methods of RM melting were tested by introducing the main alloying elements and impurities. The RM homogeneity study was carried out, and it was found that the homogeneity characteristic of Sн for alloying elements is less than 1 % of the certified value, which suggests a good distribution of elements in the bulk. The study of the RM chemical composition showed that the content of elements varies and allows the RM application for calibration of spectral equipment. Calibration dependences are constructed based on optical-emission and X-ray fluorescence analyzers. Dependences are linear, which makes it possible to apply RM for calibration of spectral equipment. The developed RM is appropriate for the optical-emission method of analysis, which does not include the dissolution of samples in acids. This allows to reduce labor intensity compared to the inductively coupled plasma atomic emission method by ~3 times and energy consumption by ~3.5 times.As a result of the study, a set of certified reference materials was developed for the spectral analysis of the VSDP-16 aluminum alloy GSO 11696–2021, the certified values of which are traceable to the unit of mass fraction by direct measurements on the State Primary Standard of units of mass (molar) fraction and mass (molar) concentration of components in liquid and solid substances and materials based on spectral methods GET 196-2015.

Reference Materials for the Activity Concentration of Technogenic Radionuclides and the Mass Fraction of Elements Based on the Soil Matrix of the Semipalatinsk Test Site

The application of reference materials for the composition and properties of natural objects with certified characteristics is the main instrument for ensuring the correctness of the obtained analytical information in radioecological, geological, and other studies. The article presents the experience of the branch of the Institute of Radiation Safety and Ecology of the National Nuclear Center of the Republic of Kazakhstan in the development and certification of reference materials containing technogenic radionuclides and mass fractions of elements. The soil selected from the sites of underground and surface nuclear tests at the «Experimental field» and «Balapan» sites of the former Semipalatinsk Test Site, which has a diverse radionuclide composition (natural and technogenic radionuclides) with a wide range of chemical elements, was chosen as the starting material for production of reference materials. The main purpose of the work is the certification of two reference materials: reference material for the activity concentration of 137Cs, 90Sr, the mass fraction of Zn, Cu, Pb, Cd, Co, Fe, Mn, As in the soil cover of the Semipalatinsk Test Site (KZ.04.01.00007–2020) and reference material for the activity concentration of 152Eu, 60Co, the mass fraction of Zn, Cu, Pb, Cd, Co, Fe, Mn, As in the soil cover of the Semipalatinsk Test Site (KZ.04.01.00008–2020).All procedures necessary for the creation of reference materials were carried out: separation of the magnetic fraction from the bulk of the material, grinding of the material, control sieve of the material, as well as homogenization with subsequent analytical studies to certify the parameters of reference materials. The methods of gamma spectrometry, beta spectrometry, mass spectrometry, and combined measurement results processing were applied. The results of an interlaboratory comparative test to determine the certified value of the concentrations of the specified radionuclides and elements are given.Reference materials are soil samples dried to an air-dry state, grinded to a particle size of less than 60 µm, and packaged in hermetically sealed polypropylene containers weighing 200 g. Reference materials have been included in the register of the state system for ensuring the uniformity of measurements and approved as state reference materials of the Republic of Kazakhstan. The scope of reference materials is to provide interlaboratory quality control of tests of analytical laboratories specialized in conducting radioecological complex studies, as well as the development and validation of analytical measurement procedures.

VALCOR: a protocol for the validation of SARS-corona virus-2 assays

BackgroundTesting for SARS-CoV-2, together with vaccination, is one of the most vital strategies in curbing the current COVID-19 pandemic. The pandemic has led to an unprecedented need for diagnostic testing and the rapid emergence of an abundance of commercial assays on the market. Due to the nature of the pandemic and in the interest of health protection, many of these assays received provisional authorisation for emergency use without thorough validation. To limit false negative and false positive results, it is key to define common criteria that SARS-CoV-2 assays need to fulfil. VALCOR or “VALidation of SARS-CORona Virus-2 assays” is a protocol designed to set up a framework for test validation of SARS-CoV-2 virus assays.ObjectivesVALCOR is a study protocol for the validation of assays used for confirmation of the presence of SARS-CoV-2 in patients with COVID-19 disease or the screening of carriers of SARS-CoV-2 virus by the identification of viral RNA in oropharyngeal and/or nasopharyngeal specimens or other specimens from the human respiratory tract.MethodsThe VALCOR panel of samples will contain clinical human specimens and standardised artificial specimens. The collection of clinical specimens will include nasopharyngeal or oropharyngeal specimens or other specimens from the respiratory tract obtained from COVID-19 patients and healthy carriers of SARS-CoV-2 as well as specimens from subjects not carrying SARS-CoV-2. Artificial specimens include calibrated amounts of viral RNA of SARS-CoV-2 sequences provided by established competent agencies that produce reference materials for the assessment of the limit of detection of each assay. The panel of samples are sent from a central reference laboratory (having access to biobanks of clinical specimens tested already for SARS-CoV-2 with a reference comparator assay) to participating laboratories for testing with a SARS-CoV-2 index assay that requires evaluation.DiscussionVALCOR provides a harmonised and standard framework to benchmark the testing performance of SARS-CoV-2 assays that are rapidly evolving. As the pandemic incited an urgent need for testing capacity, there is a gap in the comprehensive validation of SARS-CoV-2 assays. This study will generate comprehensive validation data for assays used for the diagnosis of SARS-CoV-2 and may serve as a basis for other validation protocols.

Trends in selected fields of reference material production

For more than 110 years, BAM has been producing reference materials for a wide range of application fields. With the development of new analytical methods and new applications as well as continuously emerging more stringent requirements of laboratory accreditation with regard to quality control and metrological traceability, the demand and requirements for reference materials are increasing. This trend article gives an overview of general developments in the field of reference materials as well as developments in selected fields of application in which BAM is active. This includes inorganic and metal analysis, gas analysis, food and consumer products, and geological samples. In addition to these more traditional fields of application, developments in the areas of optical spectroscopy, particularly fluorescence methods, and nanomaterials are considered.

Study on the Production of Reference Material of Heavy Metals (As, Cd, Pb, Hg) in Water

Reference materials are an important tool in ensuring the validity of testing results. The use of standard materials in Vietnam is currently limited because the supply depends on foreign standard material manufacturers at a high cost, and there is no domestic manufacturer for water and food reference materials production. This study aims to provide a procedure reference materials production for heavy metals Pb, Cd, As, and Hg analysis in water. The reference materials were homogenized and stable for a period of 318 days from the date of manufacture. With the assigned values consistent with the concentration to be analyzed of the heavy metals in the normal water sample. The measurement uncertainty ranges from 7.0 to 21.7 %. These reference materials can be used for internal quality control for laboratories. The research provides a standard procedure for the following production times for reference materials for heavy metal analysis in water and also a premise for further research on standard samples with matrix and other analytical criteria.

Creation of and first meeting of the new ISO technical committee for reference materials (ISO/TC 334)

On 14 December 2020, the ISO Technical Management Board (TMB) took the decision to transform ISO/REMCO, the ISO Committee for Reference Materials, and to create a new technical committee (ISO/TC 334). The main reason for this decision was to facilitate the transformation of the ISO/REMCO Guides, developed for the production and use of reference materials, into other ISO deliverables, most probably international standards. The inaugural meeting of the committee took place on 8 and 9 September 2021 and the resolutions from the first meeting was approved at a subsequent meeting on 16 November 2021. The most important decisions that were taken during this meeting included the approval of the title and scope of work of the committee and the plan of action for the transformation of the ISO/REMCO Guides into international ISO standards.

РАЗРАБОТКА СТАНДАРТНЫХ ОБРАЗЦОВ СОСТАВА МАГНИЕВОГО СПЛАВА МЛ19

The development of technology for the manufacture and production of reference materials (CRMs) of the composition of the magnesium alloy ML19 has been carried out. Manufactured material for CRM pipes with a diameter of 40 mm and a height of 30 mm. Tests of the material for CRM have been carried out in order to validate it. The metrological characteristics of the CRM were established, a metrological examination was carried out, and the conclusion on the verification of the CRM test results for the composition of the ML19 magnesium alloy.

Study on the production of Reference Material (RM) for Vitamin B1, B2, B6 in health supplements

Vitamins are essential nutrients commonly found in food products in general and health supplements in particular. In order to accurately evaluate product quality, laboratories need to use reference material in analysis, proficiency assessment, method validation and ensure the validity of the results. The use of reference materials plays an important role in the quality control of test results and is a mandatory requirement for laboratories wishing to demonstrate appropriate competence as required by ISO/IEC 17025:2017. The need to provide reference materials for laboratories is huge. However, at present, there are very few domestic organizations that can produce reference materials, while the cost of buying reference materials from reputable firms in the world is expensive. In this study, we introduced the procedure and production reference materials for the analysis of B-group vitamins (B1, B2, B6). These reference materials were evaluated for homogeneity and stability in 322 days. The certified values are consistent with the concentrations of substances present in normal samples in practice. The measurement uncertainty ranges from 14.5 - 23.3 %. The reference materials can be used for internal quality control for domestic laboratories and is also a premise for further research on standard samples with different matrix and analytical criteria.