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Interlaboratory comparison exercises for determining the gross alpha and beta activity concentrations in drinking water, organized by the National Institute for Radiological Protection (NIRP), China CDC, have been carried out since 2012. The purpose of this study is to assess the accuracy and precision of gross alpha and beta analyses of low-level radioactivity concentrations. Natural water samples were used for the comparison, and the performance of the participating laboratories was evaluated with respect to the reference values using the Z-score performance indicator. The comparison data from 2012 to 2022 were analyzed, where the percentage of laboratories with acceptable results was 80-92%, and the dispersion of the measurement results across laboratories became smaller over time. The results demonstrate that these exercises can help laboratories to resolve issues in gross α/ß analysis and improve the consistency of the measurement results.

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Phosphatidylethanol (PEth) has become an important marker to assess drinking behaviour and monitor abstinence. Despite its increasing use, knowledge on robustness and standardization and comparability of methods and results are still limited. In 2022, the first international consensus for the use of PEth and its interpretation was published. To establish an experience-based foundation for further harmonization, three rounds of interlaboratory comparison using microsamples were conducted. Participating laboratories sent their sampling devices to the laboratory of Forensic Toxicology at the University of Bern, where for each round, four different authentic blood samples were applied to the devices and sent back. The PEth 16:0/18:1 target concentrations covered a range between 16 and 474 ng/mL (0.023 and 0.676 µmol/L, respectively) and included sample concentrations close to the decision limits of 20 and 200 ng/mL (0.025 and 0.28 µmol/L, respectively). Evaluation of the results based on guidelines by Horwitz and the Society of Toxicological and Forensic Chemistry (GTFCh) showed that 73% of all participating laboratories quantified and reported all samples (N = 4 for each round) within the acceptable limits. More than 90% quantified and reported at least one sample within the acceptable limits.

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Gene panel sequencing has become a common diagnostic tool for detecting somatically acquired mutations in myeloid neoplasms. However, many panels have restricted content, provide insufficient sensitivity levels, or lack clinically validated workflows. We here describe the development and validation of the Genomic Medicine Sweden myeloid gene panel (GMS-MGP), a capture-based 191 gene panel including mandatory genes in contemporary guidelines as well as emerging candidates. The GMS-MGP displayed uniform coverage across all targets, including recognized difficult GC-rich areas. The validation of 117 previously described somatic variants showed a 100% concordance with a limit-of-detection of a 0.5% variant allele frequency (VAF), achieved by utilizing error correction and filtering against a panel-of-normals. A national interlaboratory comparison investigating 56 somatic variants demonstrated highly concordant results in both detection rate and reported VAFs. In addition, prospective analysis of 323 patients analyzed with the GMS-MGP as part of standard-of-care identified clinically significant genes as well as recurrent mutations in less well-studied genes. In conclusion, the GMS-MGP workflow supports sensitive detection of all clinically relevant genes, facilitates novel findings, and is, based on the capture-based design, easy to update once new guidelines become available. The GMS-MGP provides an important step toward nationally harmonized precision diagnostics of myeloid malignancies.

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BACKGROUND: Chlorinated 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. RESULTS: We 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 NOVELTY: The 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.

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Data and results from interlaboratory comparison (ILC) studies, external quality assessment (EQA) and proficiency testing (PT) activities are important and valuable contributions both to the further development of all disciplines of medical laboratory diagnostics, and to the evaluation and comparison of in vitro diagnostic assays. So far, however, there are no recommendations as to which essential items should be addressed in publications on interlaboratory comparisons. The European Organization of External Quality Assurance Providers in Laboratory Medicine (EQALM) recognized the need for such recommendations, and these were developed by a group of experts. The result of this endeavor is the EQALM Statement on items recommended to be addressed in publications on interlaboratory comparison activities (PubILC), in conjunction with a user-friendly checklist. Once adopted by authors and journals, the EQALM Statement will ensure essential information and/or study-related facts are included within publications on EQA/PT activities.

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The quality of chemical analysis is an important aspect of passive sampling-based environmental assessments. The present study reports on a proficiency testing program for the chemical analysis of hydrophobic organic compounds in silicone and low-density polyethylene (LDPE) passive samplers and hydrophilic compounds in polar organic chemical integrative samplers. The median between-laboratory coefficients of variation (CVs) of hydrophobic compound concentrations in the polymer phase were 33% (silicone) and 38% (LDPE), similar to the CVs obtained in four earlier rounds of this program. The median CV over all rounds was 32%. Much higher variabilities were observed for hydrophilic compound concentrations in the sorbent: 50% for the untransformed data and a factor of 1.6 after log transformation. Limiting the data to the best performing laboratories did not result in less variability. Data quality for hydrophilic compounds was only weakly related to the use of structurally identical internal standards and was unrelated to the choice of extraction solvent and extraction time. Standard deviations of the aqueous concentration estimates for hydrophobic compound sampling by the best performing laboratories were 0.21 log units for silicone and 0.27 log units for LDPE (factors of 1.6 to 1.9). The implications are that proficiency testing programs may give more realistic estimates of uncertainties in chemical analysis than within-laboratory quality control programs and that these high uncertainties should be taken into account in environmental assessments.

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An HPLC-MS/MS multi-class method for quantitation of 15 different classes of veterinary drug residues (>140 analytes) in milk and poultry feed was developed and validated. Accuracy criteria for routine laboratories were met for the majority of analytes, > 83 % in milk and between 50 and 60 % in chicken feed, with an apparent recovery of 60-140 %. Extraction efficiency criteria were met for >95 % of the analytes for milk and > 80 % for chicken feed. Intermediate precision meets the SANTE criterion of RSD < 20 % for 80-90 % of the analytes in both matrices. For all analytes with an existing MRL in milk, the LOQ was below the related MRL. Twenty-nine samples of commercial milk and chicken feed were analyzed within the interlaboratory comparison. No residues of veterinary drugs were found in the milk samples. However, the feed samples exhibited high levels of nicarbazin, salinomycin, and decoquinate.

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The determination of urea in pet feed at contaminant levels using the spectrophotometric method described in Commission Regulation (EC) No 152/2009 has been reported by several EU laboratories to lack the required selectivity. Whilst urea is not authorised as an additive in pet feed, the control of urea in pet feed is of economic importance, because the addition of urea may unlawfully increase the apparent protein content. To investigate the capabilities of different analytical techniques, a proficiency test was organised where the participants (EU official control laboratories, laboratories from the academia and private laboratories) were free to use their method of choice for analysing three dog feed test materials, two samples of which were spiked with urea. Twenty-one laboratories submitted results using the following techniques: spectrophotometry (Implementing Regulation (EC) No 152/2009), LC-MS/MS, HPLC-UV, enzymatic-colorimetry, gravimetry and an 'in-house photometric' method. Only two laboratories that used LC-MS/MS were able to quantify urea accurately in the test material containing a mass fraction of 18.9 mg kg-1 whereas satisfactory results at the level of 258.9 mg kg-1 were obtained by one participant that used an 'in-house photometric method' and one that used the enzymatic method, in addition to the five participants using LC-MS/MS. The technique that provided the highest success rate across the three test materials was LC-MS/MS, whereas spectrophotometry, the enzymatic-based and HPLC-UV methods led to overestimated results in addition to a dispersion of results not suitable for compliance analysis. To address the determination of urea in pet feed at low levels, a better performing method than the one described in the legislation is required.

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The recently introduced unified pH ([Formula: see text]) concept enables rigorous pH measurements in non-aqueous and mixed media while at the same time maintaining comparability to the conventional aqueous pH scale. However, its practical application is hindered by a shortage of reference [Formula: see text] values. In order to improve this situation, the European Metrology Research Project (EMPIR) UnipHied ("Realisation of a UnipHied pH scale") launched an interlaboratory comparison among highly experienced electrochemistry expert laboratories to assign the first such reference [Formula: see text] values by adopting an extensive statistical treatment of the reported measurement data: to phosphate buffer in water-ethanol mixture (50 wt% of ethanol) and ammonium formate buffer in pure ethanol. Two different measurement setups - one capable of being easily adopted in industrial applications - have been used to demonstrate the robustness of [Formula: see text] measurement. This is an important step towards wider adoption of the [Formula: see text] concept in practice, like liquid chromatography, biofuels analysis and electrocatalysis.

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Objective To summarize and improve the related technical issues by analyzing the nationwide interlaboratory comparison of gross α and gross β radioactivity measurement over the years. Methods According to the requirements of interlaboratory comparison and the national standards, the gross α and gross β radioactivity in water were measured, and the results were analyzed to identify the influencing factors. Results From 2018 to 2022, our laboratory participated in five nationwide interlaboratory comparisons of gross α and gross β radioactivity measurement. The Z-test values for gross α and gross β measurement ranged from −0.24 to 1.8 and −1.4 to 0.35, respectively. The relative deviations ranged from −4% to 32% and −18% to 6%, respectively. All comparisons were within the acceptable ranges. Conclusion The analysis of comparisons showed that the results were within the acceptable ranges. The relative deviations between the measurement and the reference values have decreased over the years. The summary and improvement of related technologies have improved the measurement accuracy.

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Research on per- and polyfluoroalkyl substances (PFAS) frequently incorporates organofluorine measurements, particularly because they could support a class-based approach to regulation. However, standardized methods for organofluorine analysis in a broad suite of matrices are currently unavailable, including a method for extractable organofluorine (EOF) measured using combustion ion chromatography (CIC). Here, we report the results of an international interlaboratory comparison. Seven laboratories representing academia, government, and the private sector measured paired EOF and PFAS concentrations in groundwater and eel (Anguilla rostrata) from a site contaminated by aqueous film-forming foam. Among all laboratories, targeted PFAS could not explain all EOF in groundwater but accounted for most EOF in eel. EOF results from all laboratories for at least one replicate extract fell within one standard deviation of the interlaboratory mean for groundwater and five out of seven laboratories for eel. PFAS spike mixture recoveries for EOF measurements in groundwater and eel were close to the criterion (±30%) for standardized targeted PFAS methods. Instrumental operation of the CIC such as replicate sample injections was a major source of measurement uncertainty. Blank contamination and incomplete inorganic fluorine removal may introduce additional uncertainties. To elucidate the presence of unknown organofluorine using paired EOF and PFAS measurements, we recommend that analysts carefully consider confounding methodological uncertainties such as differences in precision between measurements, data processing steps such as blank subtraction and replicate analyses, and the relative recoveries of PFAS and other fluorine compounds.

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Wastewater-based SARS-CoV-2 epidemiology (WBE) has proven as an excellent tool to monitor pandemic dynamics supporting individual testing strategies. WBE can also be used as an early warning system for monitoring the emergence of novel pathogens or viral variants. However, for a timely transmission of results, sophisticated sample logistics and analytics performed in decentralized laboratories close to the sampling sites are required. Since multiple decentralized laboratories commonly use custom in-house workflows for sample purification and PCR-analysis, comparative quality control of the analytical procedures is essential to report reliable and comparable results. In this study, we performed an interlaboratory comparison at laboratories specialized for PCR and high-throughput-sequencing (HTS)-based WBE analysis. Frozen reserve samples from low COVID-19 incidence periods were spiked with different inactivated authentic SARS-CoV-2 variants in graduated concentrations and ratios. Samples were sent to the participating laboratories for analysis using laboratory specific methods and the reported viral genome copy numbers and the detection of viral variants were compared with the expected values. All PCR-laboratories reported SARS-CoV-2 genome copy equivalents (GCE) for all spiked samples with a mean intra- and inter-laboratory variability of 19 % and 104 %, respectively, largely reproducing the spike-in scheme. PCR-based genotyping was, in dependence of the underlying PCR-assay performance, able to predict the relative amount of variant specific substitutions even in samples with low spike-in amount. The identification of variants by HTS, however, required >100 copies/ml wastewater and had limited predictive value when analyzing at a genome coverage below 60 %. This interlaboratory test demonstrates that despite highly heterogeneous isolation and analysis procedures, overall SARS-CoV-2 GCE and mutations were determined accurately. Hence, decentralized SARS-CoV-2 wastewater monitoring is feasible to generate comparable analysis results. However, since not all assays detected the correct variant, prior evaluation of PCR and sequencing workflows as well as sustained quality control such as interlaboratory comparisons are mandatory for correct variant detection.

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Anticoagulant rodenticides (ARs) are used to control rodent populations. Poisoning of non-target species can occur by accidental consumption of commercial formulations used for rodent control. A robust method for determining ARs in animal tissues is important for animal postmortem diagnostic and forensic purposes. We evaluated an ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) method to quantify 8 ARs (brodifacoum, bromadiolone, chlorophacinone, coumachlor, dicoumarol, difethialone, diphacinone, warfarin) in a wide range of animal (bovine, canine, chicken, equine, porcine) liver samples, including incurred samples. We further evaluated UPLC-MS in 2 interlaboratory comparison (ILC) studies; one an ILC exercise (ICE), the other a proficiency test (PT). The limits of detection of UPLC-MS were 0.3-3.1 ng/g, and the limits of quantification were 0.8-9.4 ng/g. The recoveries obtained using UPLC-MS were 90-115%, and relative SDs were 1.2-13% for each of the 8 ARs for the 50, 500, and 2,000 ng/g spiked liver samples. The overall accuracy from the laboratories participating in the 2 ILC studies (4 and 11 laboratories for ICE and PT studies, respectively) were 86-118%, with relative repeatability SDs of 3.7-11%, relative reproducibility SDs of 7.8-31.2%, and Horwitz ratio values of 0.5-1.5. Via the ILC studies, we verified the accuracy of UPLC-MS for AR analysis in liver matrices and demonstrated that ILC can be utilized to evaluate performance characteristics of analytical methods.

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Background: Medical device manufacturers are obliged to prove the biocompatibility of their products when they come into contact with the human body. The requirements for the biological evaluation of medical devices are specified by the international standard series ISO 10993. Part five of this series describes the performance of in vitro cytotoxicity tests. This test evaluates the effects of medical device use on cell health. The existence of the specific standard suggests that the tests will produce reliable and comparable results. However, the ISO 10993-5 offers wide latitude in the test specifications. In the past, we noticed inconsistencies of the results from different laboratories. Objective: To determine if the specifications of the standard ISO 10993-5 are explicit to ensure the comparability of test results and, if not, identify potential influencing factors. Methods: An interlaboratory comparison was conducted for the in vitro cytotoxicity test according to ISO 10993-5. Fifty-two international laboratories evaluated the cytotoxicity for two unknown samples. One was polyethylene (PE) tubing, which is expected to be non-cytotoxic and the other was polyvinyl chloride (PVC) tubing, for which a cytotoxic potential was presumed. All laboratories were asked to perform an elution test with predefined extraction specifications. The other test parameters were freely chosen by the laboratories according to the guidelines set by the standard. Results: To our surprise only 58 percent of the participating laboratories identified the cytotoxic potential of both materials as expected. Particularly for PVC a considerable variation of the results between the laboratories was observed [mean = 43 ± 30 (SD), min = 0, max = 100]. We showed that ten percent serum supplementation to the extraction medium, as well as longer incubation of the cells with the extract, greatly increased the test sensitivity for PVC. Conclusion: The results clearly show that the specifications set by the ISO 10993-5 are not explicit enough to obtain comparable results for an identical medical device. To set requirements that ensure reliable cytotoxicity assessments, further research will be necessary to identify the best test conditions for specific materials and/or devices and the standard needs to be revised accordingly.

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Concentrations of extracellular vesicles (EVs) in body fluids are being explored as disease biomarkers. Most laboratories use flow cytometry to characterize single EVs at high throughput. A flow cytometer (FCM) detects light scattering and fluorescence intensities of EVs. However, detection of EVs by flow cytometry is complicated for 2 reasons. First, EVs are small and have weak light scattering and fluorescence signals compared to cells and are, therefore, hard to detect. Second, FCMs differ in sensitivity and provide data in arbitrary units, which complicates data interpretation. Due to the mentioned challenges, the measured concentration of EVs by flow cytometry is cumbersome to compare between FCMs and institutes. To improve comparability, standardization and development of traceable reference materials to calibrate all aspects of an FCM are needed, as are interlaboratory comparison studies. Within this article, we will provide an overview of the standardization of EV concentration measurements, including the current effort to introduce robust calibration of FCMs, thereby enabling comparable concentration measurements of EVs, which in turn can be used to establish clinically relevant reference ranges of EV concentrations in blood plasma and other body fluids.

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A ring trial among five European laboratories was organized to reach consistency in microsatellite (MS) typing of the zoonotic parasite Toxoplasma gondii. Three sample sets were circulated and analyzed by each laboratory following a previously published method that is based on fragment length polymorphism of 15 MS markers. The first sample set compared typing results in general and focused on effects of DNA concentration; the second sample set focused on the polymorphic fingerprinting markers that can differentiate T. gondii strains within the same archetypal lineage; and the third set focused on non-archetypal genotypes. Methodological variations between laboratories, including the software programs used to determine MS fragment length, were collated using a questionnaire. Overall, lineage-level typing results reached a high level of agreement, especially in samples with the highest DNA concentrations. However, laboratory-specific differences were observed for particular markers. Major median differences in fragment length, of up to 6 base pairs, were related to the fluorophore used to label fragment-specific primers. In addition, primer pairs with identical sequences obtained from different suppliers resulted in fragments of differing length. Furthermore, differences in the way the sequencing profiles were assessed and interpreted may have led to deviating results in fragment length determination. Harmonization of MS typing, for example, by using the same fluorophores or by numerical adjustments applied to the fragment-lengths determined, could improve the uniformity of the results across laboratories. This is the first interlaboratory comparison, providing guidelines (added as a supplement) for the optimization of this technique.

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Direct comparison of high-resolution mass spectrometry (HRMS) data acquired with different instrumentation or parameters remains problematic as the derived lists of molecular species via HRMS, even for the same sample, appear distinct. This inconsistency is caused by inherent inaccuracies associated with instrumental limitations and sample conditions. Hence, experimental data may not reflect a corresponding sample. We propose a method that classifies HRMS data based on the differences in the number of elements between each pair of molecular formulae within the formulae list to preserve the essence of the given sample. The novel metric, formulae difference chains expected length (FDCEL), allowed for comparing and classifying samples measured by different instruments. We also demonstrate a web application and a prototype for a uniform database for HRMS data serving as a benchmark for future biogeochemical and environmental applications. FDCEL metric was successfully employed for both spectrum quality control and examination of samples of various nature.

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Reference materials (RMs) are vital tools in the validation of methods used to detect environmental pollutants. Microplastics, a relatively new environmental pollutant, require a variety of complex approaches to address their presence in environmental samples. Both interlaboratory comparison (ILC) studies and RMs are essential to support the validation of methods used in microplastic analysis. Presented here are results of quality assurance and quality control (QA/QC) performed on two types of candidate microplastic RMs: dissolvable gelatin capsules and soda tablets. These RMs have been used to support numerous international ILC studies in recent years (2019-2022). Dissolvable capsules containing polyethylene terephthalate (PET), polyvinyl chloride (PVC), polyethylene (PE), and polystyrene (PS), in different size fractions from 50 to 1000 µm, were produced for one ILC study, obtaining relative standard deviation (RSD) from 0 to 24%. The larger size fraction allowed for manual addition of particles to the capsules, yielding 0% error and 100% recovery during QA/QC. Dissolvable capsules were replaced by soda tablets in subsequent ILC studies and recovery test exercises because they were found to be a more reliable carrier for microplastic RMs. Batches of soda tablets were produced containing different single and multiple polymer mixtures, i.e., PE, PET, PS, PVC, polypropylene (PP), and polycarbonate (PC), with RSD ranging from 8 to 21%. Lastly, soda tablets consisting of a mixture of PE, PVC, and PS (125-355 µm) were produced and used for recovery testing during pretreatment of environmental samples. These had an RSD of 9%. Results showed that soda tablets and capsules containing microplastics >50 µm could be produced with sufficient precision for internal recovery tests and external ILC studies. Further work is required to optimize this method for smaller microplastics (< 50 µm) because variation was found to be too large during QA/QC. Nevertheless, this approach represents a valuable solution addressing many of the challenges associated with validating microplastic analytical methods.

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BACKGROUND: Accurate and reliable measurement of human serum free thyroxine (FT4) is critical for the diagnosis and treatment of thyroid diseases. However, concerns have been raised regarding the performance of FT4 measurements in patient care. Centers for Disease Control and Prevention Clinical Standardization Programs (CDC-CSP) address these concerns by creating a FT4 standardization program to standardize FT4 measurements. The study aims to develop a highly accurate and precise candidate Reference Measurement Procedure (cRMP), as one key component of CDC-CSP, for standardization of FT4 measurements. METHODS: Serum FT4 was separated from protein-bound thyroxine with equilibrium dialysis (ED) following the recommended conditions in the Clinical and Laboratory Standards Institute C45-A guideline and the published RMP [20,21,23]. FT4 in dialysate was directly quantified with liquid chromatography-tandem mass spectrometry (LC-MS/MS) without derivatization. Gravimetric measurements of specimens and calibrator solutions, calibrator bracketing, isotope dilution, enhanced chromatographic resolution, and T4 specific mass transitions were used to ensure the accuracy, precision, and specificity of the cRMP. RESULTS: The described cRMP agreed well with the established RMP and two other cRMPs in an interlaboratory comparison study. The mean biases of each method to the overall laboratory mean were within ±2.5%. The intra-day, inter-day, and total imprecision for the cRMP were within 4.4%. The limit of detection was 0.90 pmol/L, which was sufficiently sensitive to determine FT4 for patients with hypothyroidism. The structural analogs of T4 and endogenous components in dialysate did not interfere with the measurements. CONCLUSION: Our ED-LC-MS/MS cRMP provides high accuracy, precision, specificity, and sensitivity for FT4 measurement. The cRMP can serve as a higher-order standard for establishing measurement traceability and provide an accuracy base for the standardization of FT4 assays.

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Flake thickness is one of the defining properties of graphene-related 2D materials (GR2Ms), and therefore requires reliable, accurate, and reproducible measurements with well-understood uncertainties. This is needed regardless of the production method or manufacturer because it is important for all GR2M products to be globally comparable. An international interlaboratory comparison on thickness measurements of graphene oxide flakes using atomic force microscopy has been completed in technical working area 41 of versailles project on advanced materials and standards. Twelve laboratories participated in the comparison project, led by NIM, China, to improve the equivalence of thickness measurement for two-dimensional flakes. The measurement methods, uncertainty evaluation and a comparison of the results and analysis are reported in this manuscript. The data and results of this project will be directly used to support the development of an ISO standard.