Matrix Reference Materials Research Articles

Investigating the metabolism of four sulfonamides in grass carp via HPLC-MS for screening candidate materials of matrix reference material

An efficient, sensitive, and precise method for investigating the metabolism of four sulfonamides in grass carp has been established using high-performance liquid chromatography-mass spectrometry. By optimizing the experimental conditions, the method achieved a coefficient of determination above 0.999, with detection and quantification limits set at 0.5 μg/kg and 1.0 μg/kg, respectively. Recovery rates were between 92.90 % and 102.84 %, and relative standard deviations ranged from 1.70 % to 9.83 %, enabling the precise detection of these sulfonamides in grass carp tissue. The factors affecting the metabolic rate during the medicated bath process were investigated, and obtained the optimal parameter conditions for screening the candidate materials. The candidate materials screened through this method exhibit good stability when used to prepare matrix standard substances, this work not only provides a scientific basis for screening sulfonamide candidate materials but also offers insights for developing other matrix reference materials.

Reference Material for the Composition of Fuel Oil

Electrical transformers are a key element in the process of distributing electricity from the producer to the final consumer. The reliability of electrical transformers is ensured through systematic monitoring of the structural condition using chemical analysis of fuel (transformer) oil used for electrical insulation and cooling of transformers. The working life of energy oil and paper insulation can be assessed by evaluating the content of antioxidant additive (ionol) and furan derivatives (furfuryl alcohol, furfural, 2-acetylfuran and 5-methylfurfural). The article provides a critical analysis of methods for measuring ionol and furan derivatives in oils. In particular, it has been established that the most widely used methods for the identification of ionol and furan derivatives are liquid and gas chromatography methods with preliminary isolation of analytes based on the principles of liquid/solid-phase extraction. At the same time, the need for matrix reference materials with established metrological traceability was identified for metrological support of methods for measuring the content of ionol and furan derivatives in oils. Therefore, the purpose of this study was the development of a certified reference material (CRM) for the composition of fuel oil. The technology for producing such a CRM makes it possible to prepare the material with the required concentrations of analytes. The article describes the sequence of preparation of a CRM batch and presents the conclusions of studying the stability and between-bottle homogeneity of the material. The given calculation of the standard uncertainty for the certified value of the CRM from the characterization method, heterogeneity, and instability of the material in accordance with GOST ISO Guide 35–2015 deserves attention. The metrological traceability of certified values of the CRM to the unit of value «mass fraction of a component» reproduced by the State Primary Standard of units of mass (molar) fraction and mass (molar) concentration of organic components in liquid and solid substances and materials based on liquid and gas chromatography-mass spectrometry with isotope dilution and gravimetry (GET 208–2019). The competence of the study is confirmed by the fact that the CRM was recognized as GSO 12232–2023.

Repeated lyophilization: A neo-method for urine-based reference materials preparation

In urine drug testing, a cut-off value is often imposed to determine whether the sample is negative or positive. A matrix containing a reference substance helps counteract the adverse effects of the urine matrix across different laboratories to improve the consistency of final results. However, as a biological matrix, urine is prone to corruption and other problems that make it difficult to use as a reference sample. In this study, morphine, nitrazepam, lorazepam, buprenorphine, zolpidem, midazolam, diazepam, and clozapine commonly used in clinical practice were selected as target analytes, and the preparation process was further optimized to repeated lyophilization, in order to obtain more effective, stable, and accurate urine matrix reference materials (mRMs). The appropriate urine density (1.010–1.017 kg/m3) for preparing lyophilized samples was investigated through density determination. Conducting repeated lyophilizations resulted in a denser powder with reduced susceptibility to collapse and improved the quality of lyophilized urine samples. Lyophilized urine mRMs could be stored at room temperature for one month or under refrigeration conditions (4 ℃) for six months.

A method for simultaneously and accurately quantify seven quinolones in matrix reference materials by HPLC-MS

Reference materials (RM) are commonly employed in analytical chemistry for tasks such as instrument calibration, validation of analytical methods and quality control. Determining the values of target drugs in the matrix is a key step in the development of matrix reference materials. However, there is almost no sharing of the certification methodologies for the development of RM. Hence, a detailed method was established for the value determination of seven quinolones in minced fish matrix, which was the candidate materials for preparing matrix reference materials. Target analysis of quinolone drugs in complex matrix was performed by “quick, easy, cheap, effective, rugged and safe” (QuEChERS) extraction and high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS). The accuracy, precision, and sensitivity of this method has been thoroughly validated, which provided a robust analytical tool for the accurate quantification of quinolones in quality control samples and actual samples with a detection limit of 0.5–0.6 μg/kg and a quantification limit of 1 μg/kg. The actual samples prepared by three different spiking methods was determined, the outstanding performance show that this method contributing significantly to the development of matrix reference materials in aquatic products, which can be used as a template for the determination of other quinolone compounds in minced fish matrix. This work can not only provide reference for the development of matrix reference materials, but also promote the development of metrology.

Study of New CGSP‐P Series Phosphate Matrix Reference Materials for LA‐ICP‐MS

A series of three CGSP‐P phosphate matrix reference materials, with variable element mass fractions, were synthesised by co‐precipitation with CaCl2 and (NH4)3PO4 to form a hydroxylapatite matrix. Each powder sample was packaged into multiple bottles and pressed into tablets as replicates. The within‐bottle homogeneity was evaluated by the repeatability of element mass fractions of six spots in per tablet of CGSP‐Ps by LA‐ICP‐MS. For the between‐bottle homogeneity evaluation, one approach adopted the % RSD of element mass fractions in twelve different tablets from twelve bottles in the same reference material in comparison with the repeatability field of LA‐ICP‐MS analyses obtained from homogeneous glasses, and the other used a one‐way analysis of variance (ANOVA) approach. Most of the elements (e.g., Mg, Ca, P, Mn and REE) were homogenous within 10% RSD, and other elements (e.g., Si, Al, K, Rb, Cs and Ni) were considered heterogeneous (with > 20% RSD). All of the elements passed the t‐test except Ni in CGSP‐P3, and V, Cr, Ni, Zr, Gd, Dy and Th in CGSP‐P4 after a 29‐month period stability examination by LA‐ICP‐MS. The preliminary reference values and standard uncertainties for CGSP‐Ps are given with a network of methods and eight laboratories by bulk analysis according to ISO Guide 35:2006 and JJF 1343‐2012.

Stepping-up accurate quantification of chlorinated paraffins: Successful certification of the first matrix reference material

BackgroundChlorinated paraffins (CPs) are industrial chemicals categorised as persistent organic pollutants because of their toxicity, persistency and tendency to long-range transport, bioaccumulation and biomagnification. Despite having been the subject of environmental attention for decades, analytical methods for CPs still struggle reaching a sufficient degree of accuracy. Among the issues negatively impacting the quantification of CPs, the unavailability of well-characterised standards, both as pure substances and as matrix (certified) reference materials (CRMs), has played a major role. The focus of this study was to provide a matrix CRM as quality control tool to improve the comparability of CPs measurement results. ResultsWe present the process of certification of ERM®-CE100, the first fish reference material assigned with certified values for the mass fraction of short-chain and medium-chain chlorinated paraffins (SCCPs and MCCPs, respectively). The certification was performed in accordance with ISO 17034:2016 and ISO Guide 35:2017, with the value assignment step carried out via an intercomparison of laboratories of demonstrated competence in CPs analysis and applying procedures based on different analytical principles. After confirmation of the homogeneity and stability of the CRM, two certified values were assigned for SCCPs, depending on the calibrants used: 31 ± 9 μg kg−1 and 23 ± 7 μg kg−1. The MCCPs certified value was established as 44 ± 17 μg kg−1. All assigned values are relative to wet weight in the CRM that was produced as a fish paste to enhance similarity to routine biota samples. Significance and noveltyThe fish tissue ERM-CE100 is the first matrix CRM commercially available for the analysis of CPs, enabling analytical laboratories to improve the accuracy and the metrological traceability of their measurements. The certified CPs values are based on results obtained by both gas and liquid chromatography coupled with various mass spectrometric techniques, offering thus a broad validity to laboratories employing different analytical methods and equipment.

Eco-Friendly Spiking Approach Based on Microfluidics for Preparation of Matrix Reference Materials.

Medicated bath is the most common spiking method used in the development of matrix reference materials for aquatic products; however, the environmental issues caused by the treatment of waste liquid after medicated bath cannot be ignored. We proposed an environmentally friendly spiking method based on microfluidics, which significantly improved the drug utilization rate without the need for subsequent drug residue treatment. Finely processed minced fish samples were fully mixed with quinolone drugs, and minced fish gel microspheres were prepared by microfluidic technology, utilizing the gel's water-locking function to enhance the drug-loading capacity. The results showed that this method can significantly increase the drug-loading capacity of the matrix (2.33-4.03 times) compared with the traditional spiking methods. In addition, the matrix reference material prepared by this method has good stability, and the drug concentration was adjustable and controllable.

Improving and controlling the drug loading capacity of seven quinolones in minced fish matrix based on microfluidics

Traditional spiking methods for preparing matrix reference material of aquatic products is difficult to control the drug content in the matrix, especially one matrix containing multiple drugs. Minced fish is commonly used for the preparation of matrix reference materials in aquatic products, which is a relatively complex matrix with stickiness and difficult handling. Drug loading capacity is a key factor affecting the effectiveness of matrix reference materials. Here, we proposed a new spiking approach to improve the drug loading capacity of seven quinolones based on microfluidics, simultaneously. Fresh grass carp tissue underwent grinding, fine filtration, centrifugation and reconstituted in distilled water to form a liquid sample, which was subsequently mixed with a sodium alginate solution (1 %) at a ratio of 1:1.2. The mixed solution was supplemented with seven quinolones of equal concentration, followed by the preparation of uniform fish gel microspheres using microfluidic technology. The results indicated that the recoveries of seven quinolones ranged from 82.54 % to 114.17 %, demonstrating a significant improvement in the drug loading capacity of these quinolones compared to traditional methods. Moreover, the drug concentration in the matrix can be precisely controlled. A strong linear relationship was observed between the concentration of seven quinolones in the matrix and its initial concentration, which could serve as a reference for the development of other matrix reference materials.

Certification of a novel matrix reference material for accurate measurements of aflatoxin M1 in milk powder

Certification of a novel matrix reference material for accurate measurements of aflatoxin M1 in milk powder

Development of an Ephedrine In-House Matrix Reference Material and Its Application to Doping Analysis.

Biomatrix-based reference materials (RMs) improve the quality of laboratory test results by better representing actual samples. However, a matrix RM of ephedrine (EP) for threshold substances that require accurate analysis results has not yet been developed. Therefore, this study aimed to develop an in-house matrix RM for EP and subsequently apply it to analytical procedures. During the development of the in-house matrix EP RM, the system underwent homogeneity and stability studies. Additionally, it was subjected to interlaboratory comparison study in 11 laboratories, including 10 World Anti-Doping Agency (WADA)-accredited laboratories and our laboratory. Stability testing revealed no significant changes in the RM characteristics. For homogeneity, 10 random batches out of 200 were analyzed to confirm the uniformity within and between bottles. These results, combined with data from 11 laboratories, ensured retroactive validation. The traceability value of the in-house matrix EP RM was assigned as 9.83 ± 0.57 μg/mL (k = 2) by interlaboratory comparison studies and traceable uncertain evaluation. The feasibility of this method as a single calibration standard was confirmed in two laboratories. This substance is reliable and consistent for quality control during EP quantification, ensuring accurate and trustworthy outcomes. Consequently, this study establishes a framework and guidelines for producing in-house matrix RMs and serves as a reference for generating similar matrix RMs in other contexts.

Development of new matrix reference materials for quantitative urine analysis in drug tests.

Accurate quantitative analyses require standardized methods to control and improve the analytical process in the laboratory. The availability of urine reference materials (RMs) may offer a feasible option to improve the accuracy of urine analysis and to control matrix effects. This paper presents the complete process of the development of matrix RMs in urine, including sample preparation, homogeneity, and stability studies, as well as uncertainty assessment. A freeze-drying process was developed, and freeze-dried human and pig urine samples were prepared and verified to have comparable homogeneity to liquid samples and higher stability than liquid human, pig, and artificial urine samples at 4℃ or room temperature and under extreme conditions. A total of 21 authentic urine samples from August 2022 were measured with freeze-dried RMs and spiked urine samples, and the reliability of the quantification of the RMs was compared. The freeze-dried human urine matrix RM appeared to be an excellent tool for daily quality control, as it showed high stability and gave the most consistent results with spiked samples.

Ochratoxin A case study: Establish metrological traceability of mycotoxin measurements using certified reference materials.

For the US Food and Drug Administration's (FDA) mycotoxin program, the desired application of certified reference materials (CRMs) is primarily for validating methods for the determination of mycotoxins in foods and establishing metrological traceability of measurement results generated by such validated methods. The latter has been an important but insufficiently addressed challenge due to the lack of appropriate protocols and CRMs. Taking advantage of two recently available mycotoxin CRMs, OTAN-1 and Standard Reference Material (SRM) 1565, a protocol was developed for systematically examining uncertainty and establishing metrological traceability of measurement results of ochratoxin A (OTA) in corn through a series of calibration operations using the two CRMs. Instrument and method calibrations were performed using OTAN-1 and SRM 1565. The OTA value and its standard and expanded (k=2, approximately 95% confidence) uncertainties were estimated from the calibration data and documented. These results demonstrate that the major contributing source of uncertainty is the sample matrix, highlighting the important role of the certified matrix reference material in method calibration. The value of OTA (38.5±7.2µg/g; 95% confidence interval) in the incurred sample was metrologically traceable to the International System of Units through two CRMs using the multi-laboratory validated liquid chromatography-mass spectrometry FDA compendial method. In addition, an alternative estimation of uncertainty was conducted using a one-point calibration, resulting in comparable uncertainty.

Paving the way for new and challenging matrix reference materials—particle suspensions at the core of material processing providing RMs for method development and method validation

Sufficient homogeneity of the certified parameter(s) over the whole fill series of a matrix reference material (RM) is a fundamental quality criterion. In practice, the heterogeneity of the target parameter is evaluated, whereby a relative value can be calculated of how much the target parameter is varying over the RM-batch. A high degree of homogeneity (low heterogeneity) is an inherent quality mark of a good RM. Here, we report how challenging matrix RMs were produced by using particle suspensions at the core of the material processing step. The examples of matrix RMs produced span from whole water reference materials for persistent organic pollutants, PM2.5-like atmospheric dust certified for specific ions to microplastic RMs. Most of these RMs were subsequently used in different phases of analytical method development or for method validation. Common to all these matrices is that they cannot be easily mixed, handled, or dosed to prepare larger sample batches. In all cases, a continuously stirred suspension of particles was used during material processing. In general, relative between-bottle heterogeneities from 1.6 to 6% were achieved for the target parameters in these matrix presentations. Concerning developments of new CRMs in emerging fields, the co-dependence between the availability of validated analytical methods with good repeatability and testing materials with a known and high homogeneity of the target parameter(s) becomes particularly challenging. This situation is an RM/Method causality dilemma. To overcome that hurdle, strategies are proposed for stepwise processes where RM producers and a network of analytical method developers could work hand in hand. In addition, development of a portfolio of inexpensive and well-homogenised common samples coupled with a reporting interface is suggested. This would benefit method developers and RM producers alike. As more and more data is compiled for a specific matrix, it paves the way for new and challenging RMs that can later be used by a wider community.

A comparative analysis of different hair matrixes and matrix reference materials for quantitative hair analysis in drug tests

The proposal of the concept of Precision Science and the rapid development of technology have raised expectations for a higher demand for accurate quantitative analysis, including hair analysis in drug tests. Many details are presently constraining improvements in precision, so there is a greater need for standardized methods to control and improve the analytical process in the laboratory. Hair matrix reference materials may become a feasible option. In the present study, 34 drug-free hair samples from healthy volunteers were collected and compared with 2 certified standard hair samples. It was observed that the hair matrix of different origins did have a significant impact on hair analysis. Three reference materials were prepared using spiking and two soaking methods, and one natural reference material was collected from real cases. A total of 57 authentic hair samples were measured from March to August 2022 using these 4 reference materials. Differences in the origins of samples were found to have a significant impact on the hair analysis results. The reference material soaked in water and methanol at a 1:1 ratio (v/v) appeared to be an excellent tool for daily quality control, as it gave results closest to those of the natural matrix reference material in all aspects and supported the law principle of the Presumption of Innocence.

Quantification of Ergot Alkaloids via Lysergic Acid Hydrazide-Development and Comparison of a Sum Parameter Screening Method.

Ergot alkaloids are a group of mycotoxins occurring in products derived from various grasses (e.g., rye) and have been regulated in the EU recently. The new maximum levels refer to the sum of the six most common ergot alkaloids in their two stereoisomeric forms in different food matrices. Typically, these twelve compounds are individually quantified via HPLC-MS/MS or -FLD and subsequently summed up to evaluate food safety in a time-consuming process. Since all these structures share the same ergoline backbone, we developed a novel sum parameter method (SPM) targeting all ergot alkaloids simultaneously via lysergic acid hydrazide. After extraction and clean-up, in analogy to the current European standard method EN 17425 (ESM) for ergot alkaloid quantitation, the samples were derivatized by an optimized hydrazinolysis protocol, which allowed quantitative conversion after 20 min at 100 °C. The new SPM was evaluated against another established HPLC-FLD-based method (LFGB) and the HPLC-MS/MS-based ESM using six naturally contaminated rye and wheat matrix reference materials. While the SPM provided comparable values to the ESM, LFGB showed deviating results. Determined recovery rates, limits of detection and quantification of all three employed methods confirm that the new SPM is a promising alternative to the classical approaches for ergot alkaloid screening in food.

An Electrochemical Sensor for the Determination of Trace Concentrations of Cadmium, Based on Spherical Glassy Carbon and Nanotubes.

The practical application of a novel, eco-friendly electrochemical sensor based on low-dimensional structures, spherical glassy carbon microparticles, and multiwall carbon nanotubes is described. This sensor, modified with a bismuth film, was used for the determination of Cd(II) by the anodic stripping voltammetric method. The instrumental and chemical factors influencing the sensitivity of the procedure were thoroughly investigated and their most favorable values were selected (acetate buffer solution pH = 3 ± 0.1; 0.15 mmol L-1 Bi(III); activation potential/time: -2 V/3 s; accumulation potential/time: -0.9 V/50 s). Under the selected conditions, the method exhibited linearity in the range of 2 × 10-9 to 2 × 10-7 mol L-1 Cd(II) with a detection limit of 6.2 × 10-10 mol L-1 Cd(II). The results obtained also showed that the application of the sensor for Cd(II) detection did not experience any significant interference in the presence of a number of foreign ions. The applicability of this procedure was evaluated using TM-25.5 Environmental Matrix Reference Material and SPS-WW1 Waste Water Certified Reference Material as well as river water samples through addition and recovery tests.

Metrological traceability of matrix reference materials

Establishment and demonstration of the metrological traceability of measurement results is one of the main goals of testing laboratories. In physicochemical measurements, the problem of establishing metrological traceability is still far from being solved and is very relevant. One of the basic principles of quantitative chemical analysis, as well as other types of measurements, is to ensure the traceability to the “standard” of the corresponding unit of physical quantity, but the unit of quantity of a substance “mole” does not have a standard. At the same time, the amount of a chemical element or stoichiometric com­pound in moles can be expressed in the units of mass — kilogram, and vice versa, the mass of any element or stoichiometric compound can be expressed in moles, using standard reference data on the atomic weight of chemical elements and their isotopes. When determining the chemical composition of matrix materials, as a rule, the mass fraction of the analyzed element (component) is determined. Algorithms for calculating the results of physical and chemical measurements are considered from the viewpoint of the metrological traceability using the example of individual methods. It is shown that the results of measure­ments of the mass fraction of elements can be traced to the standard unit of mass of SI system “kilogram.” Measuring instruments that have been verified do not always meet the requirements of GOST ISO/IEC 17025 for metrological traceability. For a significant part of universal individually calibrated analytical in­struments, the normalized metrological characteristics indicate only their capabilities and are only indi­rectly related to the uncertainty of measurements performed using these instruments. Certain difficulties are attributed to the necessity of confirming the metrological traceability of the values of certified refer­ence materials. The variants of statements on metrological traceability presented in the certificates of for­eign manufacturers of certified reference materials are considered. In conclusion, the authors provide a statement on the traceability of the certified characteristics of certified reference materials produced by ICRM.

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.

A Feasibility Study into the Production of a Mussel Matrix Reference Material for the Cyanobacterial Toxins Microcystins and Nodularins.

Microcystins and nodularins, produced naturally by certain species of cyanobacteria, have been found to accumulate in aquatic foodstuffs such as fish and shellfish, resulting in a risk to the health of the seafood consumer. Monitoring of toxins in such organisms for risk management purposes requires the availability of certified matrix reference materials to aid method development, validation and routine quality assurance. This study consequently targeted the preparation of a mussel tissue reference material incurred with a range of microcystin analogues and nodularins. Nine targeted analogues were incorporated into the material as confirmed through liquid chromatography with tandem mass spectrometry (LC-MS/MS), with an additional 15 analogues detected using LC coupled to non-targeted high resolution mass spectrometry (LC-HRMS). Toxins in the reference material and additional source tissues were quantified using LC-MS/MS, two different enzyme-linked immunosorbent assay (ELISA) methods and with an oxidative-cleavage method quantifying 3-methoxy-2-methyl-4-phenylbutyric acid (MMPB). Correlations between the concentrations quantified using the different methods were variable, likely relating to differences in assay cross-reactivities and differences in the abilities of each method to detect bound toxins. A consensus concentration of total soluble toxins determined from the four independent test methods was 2425 ± 575 µg/kg wet weight. A mean 43 ± 9% of bound toxins were present in addition to the freely extractable soluble form (57 ± 9%). The reference material produced was homogenous and stable when stored in the freezer for six months without any post-production stabilization applied. Consequently, a cyanotoxin shellfish reference material has been produced which demonstrates the feasibility of developing certified seafood matrix reference materials for a large range of cyanotoxins and could provide a valuable future resource for cyanotoxin risk monitoring, management and mitigation.

Opinion: Multi-Mycotoxin Reference Materials.

The analysis of mycotoxins in food and feed using liquid chromatography coupled with mass spectrometry is considered advantageous because the hyphenated technology enables simultaneous determination of multiple mycotoxins. Multi-mycotoxin analysis requires special consideration of quality control parameters to ensure proper evaluation of data quality for all target mycotoxins in method development and routine sample analysis. Mycotoxin matrix reference materials, especially certified reference materials, are stable and homogeneous matrices with certified traceability, concentrations, and uncertainty for mycotoxin(s) of interest. The use of these reference materials for single mycotoxin analysis has been a well-accepted practice and should be extended to multi-mycotoxin analysis. This opinion piece discusses the following essential metrological and operational components to improve data quality: (1) purposes of multi-mycotoxin reference materials; (2) comparison of reference materials, certified reference materials, and in-house quality control materials; (3) advantages of using reference materials for multi-mycotoxin analysis; (4) current trends and challenges of multi-mycotoxin reference materials. Potential applications of reference materials discussed here can improve routine mycotoxin determination and will lead to better accuracy and consistency of results. Quality control processes that incorporate reference materials in the field of mycotoxin analysis ensure successful development and implementation of liquid chromatography mass spectrometry-based multi-mycotoxin methods.