Interlaboratory Study Research Articles

FRI485 High Interlaboratory Variability In Free Thyroxine Measurement Indicates Need For Method Standardization

Abstract Disclosure: A. Ribera: None. U. Danilenko: None. O. Sugahara: None. L. Collins: None. T. Buchannan: None. N. Vazquez: None. F. Pokuah: None. D. Wirtz: None. L. Zhang: None. A.N. Lyle: None. H.W. Vesper: None. Thyroid function tests are critical to diagnose diseases of the thyroid. Concerns about the accuracy and reliability of thyroid function tests, especially free thyroxine (FT4), have been stated by the clinical laboratory community for many years. In response to these concerns, the CDC Clinical Standardization Program (CSP) has created a standardization program for FT4 based on the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference system and is partnering with IFCC to standardize FT4 and harmonize TSH testing globally. As part of this program, CDC developed an accurate and sensitive reference measurement procedure (RMP) to assign reference values to individual donor sera. Assay manufacturers and research and clinical laboratories can use these sera to assess the analytical performance of their measurements, and monitor analytical performance over time. To obtain initial information about the analytical performance of FT4 and TSH measurements, an interlaboratory study among commercial assays and laboratory developed test was conducted. A panel of 40 blinded, fresh-frozen single donor patient serum samples with FT4 concentration ranging between 11-32 pmol/L concentrations was measured by participants and compared to the results obtained by CDC RMP for FT4. In addition, commercial assay manufacturers were asked to measure thyroid-stimulating hormone (TSH). Results from sixteen commercial assays and four laboratory developed test (LDT) participated. Preliminary results indicate a negative mean bias for all commercial FT4 assays ranging from -34.46% to -5.08%. Some of the assays agreed more closely to the RMP than others (four assays had mean bias over -25%). An equilibrium dialysis mass spectrometry-based assays had mean biases ranging from -8.86% to - 1.72% agreeing well with RMP. The data suggest that the observed bias can be effectively minimized through recalibration to the RMPs operated by the CDC CSP and the IFCC reference laboratory network. The mean TSH concentrations ranged from 0.34 to 21.56 uIU/mL with mean %CV of 11.42% (95%CI 8.07%-14.76%) suggesting good agreement between various platforms. Findings from this study will be used to customize CDC’s protocols and procedures for standardizing FT4 measurements. Presentation: Friday, June 16, 2023

Multianalyte analysis of volatile compounds in virgin olive oils using SPME‐GC with FID or MS detection: results of an international interlaboratory validation

AbstractThe organoleptic assessment (Panel test) is the only procedure within the official methods for determining the quality of virgin olive oils that involves an expert panel. There is an urgent need for analytical methodology that can reliably measure volatile compounds in virgin olive oils that is capable of supporting and anticipating the official Panel test. For this reason, a new method based on solid‐phase microextraction–gas chromatography with the choice of two possible detectors (FID or MS) was subjected to a large international interlaboratory validation study. The study involved a two‐stage process: first, a pretrial phase in which 7 participants were exposed to the method for the first time to identify any initial problems with the methodology; then, a formal validation stage (trial proper), which involved 20 laboratories from Europe, USA, Japan and China. The performance of the different detectors was investigated. While both methods have advantages, the method using FID provided better results for 11 compounds, in terms of reproducibility, compared to MS. This information will allow to implement the method with accurate information of the method performance depending on the detector used.Practical applications: This study provides information from an interlaboratory validation of a method for measuring volatile compounds in virgin olive oils conducted with laboratories (from industry and academia) working in the olive oil sector. The information on the expected analytical errors in the determination of each volatile compound is necessary to apply this method for supporting the official Panel test (sensory analysis). The SPME‐GC‐MS/FID methods proposed in this work can be used for the internal quality control of a company/distributor/quality control laboratory and could also be used in cases of difficult/contradictory organoleptic assessment, or to confirm results from sensory panels in cases of disputes/disagreement (Reg. EU 2022/2105).

SAT015 Improving The Quality Of Disease Biomarker Measurements In Patient Care And Research-CDC's Clinical Standardization Programs

Abstract Disclosure: O. Sugahara: None. T. Buchannan: None. U. Danilenko: None. A. Ribera: None. L. Collins: None. N. Vasquez: None. K. Dahya: None. F. Pokuah: None. H. Zhou: None. L. Zhang: None. A.N. Lyle: None. H.W. Vesper: None. High-quality disease biomarker tests are critical for the correct diagnosis and treatment of patients, accurate interpretation of research data, and effective use of research findings in health care. CDC’s Clinical Standardization Programs (CDC CSP) assist researchers and laboratories with assessing and improving the analytical performance of biomarker tests performed in patient care, public health, and research. CDC CSP develops and applies reference methods, materials, and protocols to consistently calibrate biomarker tests across instruments and laboratories and to assess and improve other analytical performance characteristics, such as analytical specificity. CDC CSP works with test manufacturers and laboratories operating in-house developed tests to correctly calibrate tests. Additional programs help clinical and research laboratories monitor the accuracy and reliability of tests over time. Furthermore, CDC CSP collaborates with researchers on the development of reference intervals and on using new and emerging biomarkers in patient care and public health. CDC CSP provides comprehensive programs for traditional blood lipids, testosterone, estradiol, vitamin D, and free thyroxine. Programs for free testosterone, parathyroid hormones, apolipoproteins, and angiotensin peptides will be available soon. CDC CSP collaborated with members of the Partnership for the Accurate Testing of Hormones (PATH) and established reference intervals for testosterone in men. CDC CSP is currently working to develop reference intervals for testosterone in women and for estradiol in postmenopausal women. A CDC CSP interlaboratory study on free thyroxine measurements showed high variability in calibration accuracy among free thyroxine assays. CDC CSP is using its reference methods and materials to minimize this variability. It is anticipated that assay recalibration may change measurement values for some tests by up to 50%. CDC CSP is working with PATH and the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) to educate stakeholders about the upcoming change in free thyroxine measurements. Presentation: Saturday, June 17, 2023

Investigation of alternative methods for measuring and evaluating airborne sound insulation

The reproducibility of airborne noise insulation testing is poor, as documented by various interlaboratory studies. This is compounded by the definition of Sound Transmission Class (STC), the dominant single-number rating used in North America, which over-emphasizes the wall performance at and around the 125 Hz third-octave band. Small variations in performance at these frequencies can result in substantial changes in STC rating. To address these concerns, changes to both the measurement method and the single number ratings may be appropriate. For the former, the authors have begun an investigation of measuring the vibro-acoustic characteristics of walls, including measuring the vibration on the surfaces of the separating assembly and the flanking assemblies. This may result in increased precision of sound insulation measurements. For the latter issue, the authors have performed statistical evaluation of published wall sound insulation tests to clarify the effects of idiosyncrasies in the definition of STC and investigated whether different rating methods may better describe the performance of wall assemblies.

Interlaboratory study assessing the analysis of supercapacitor electrochemistry data

Supercapacitors are fast-charging energy storage devices of great importance for developing robust and climate-friendly energy infrastructures for the future. Research in this field has seen rapid growth in recent years, therefore consistent reporting practices must be implemented to enable reliable comparison of device performance. Although several studies have highlighted the best practices for analysing and reporting data from such energy storage devices, there is yet to be an empirical study investigating whether researchers in the field are correctly implementing these recommendations, and which assesses the variation in reporting between different laboratories. Here we address this deficit by carrying out the first interlaboratory study of the analysis of supercapacitor electrochemistry data. We find that the use of incorrect formulae and researchers having different interpretations of key terminologies are major causes of variability in data reporting. Furthermore we highlight the more significant variation in reported results for electrochemical profiles showing non-ideal capacitive behaviour. From the insights gained through this study, we make additional recommendations to the community to help ensure consistent reporting of performance metrics moving forward.

Moving from Raman Spectroscopy Lab towards Analytical Applications: A Review of Interlaboratory Studies

Is Raman spectroscopy applicable for analytical purposes? Although Raman spectroscopy is a commonly used technique for analyzing sample characteristics and has numerous benefits, it still has several significant limitations that hinder the current tendency to produce the same results regardless of location, equipment, or operator. Overcoming these drawbacks may help to further the development of personalized medicine, diagnosis and treatment, the development of work protocols, and the pursuit of consistent and repeatable performance across all fields. Interlaboratory studies are currently the best way to do this. In this study, we reviewed the interlaboratory studies on Raman spectroscopy conducted to highlight the importance of moving to quantitative analysis in controlled environments. The advantages of Raman spectroscopy, including its high molecular specificity, short spectrum acquisition time, and excellent component identification capabilities, were clearly stated in all experiments. The Raman spectroscopy lab is taking small steps toward analytical applications by figuring out how to accurately predict concentrations in the relevant range of concentrations, developing and verifying the technology, and producing homogenous samples for those investigations.

Polar pesticides in food of animal origin: interlaboratory validation to evaluate method fitness-for-purpose of official control

The present work reports on the design, execution and evaluation of results of an interlaboratory validation study aimed at verifying the fitness-for-purpose of a LC-MS/MS method for the detection of polar pesticides in food of animal origin in official control and monitoring programmes. To this scope, five participant laboratories, with relevant expertise, were recruited. After passing a pre-trial test, the participants were asked to analyse test samples of bovine fat, chicken eggs and cow’s milk, contaminated with 11 polar pesticides (group A: Aminomethyl phosphonic acid (AMPA), cyanuric acid, ethephon, glyphosate, fosetyl aluminium, 2-hydroxyethyphosphonic acid (HEPA), maleic hydrazide, N-acetyl-glyphosate, group B: N-acetyl glufosinate (NAG), 3-methylphosphinicopropionic acid (MPP) and glufosinate ammonium) at two different levels (0.05 and 0.25 mg/kg−1 and 0.01 and 0.05 mg/kg−1 for group A and B respectively. The method was based on acidified methanol/water extraction followed by dSPE clean up with C18 sorbent. For LC-MS/MS analysis isotopically labelled standards were used for all targeted analytes. With a couple of exceptions, average recoveries ranged from 85% to 110%, with repeatability (RSDr) ranging from 3% to 25%, and reproducibility (RSD R ) from 4% to 26%. The assessment by different laboratories provided also insights on key factors impacting method performance characteristics and its implementation by new users.

Interlaboratory evaluation of quality control methods for circulating cell-free DNA extraction

Analysis of circulating cell-free DNA (ccfDNA) isolated from liquid biopsies is rapidly being implemented into clinical practice. However, diagnostic accuracy is significantly impacted by sample quality and standardised approaches for assessing the quality of ccfDNA are not yet established. In this study we evaluated the application of nucleic acid “spike-in” control materials to aid quality control (QC) and standardisation of cfDNA isolation for use in in vitro diagnostic assays. We describe an approach for the design and characterisation of in-process QC materials, illustrating it with a spike-in material containing an exogenous Arabidopsis sequence and DNA fragments approximating to ccfDNA and genomic DNA lengths. Protocols for inclusion of the spike-in material in plasma ccfDNA extraction and quantification of its recovery by digital PCR (dPCR) were assessed for their suitability for process QC in an inter-laboratory study between five expert laboratories, using a range of blood collection devices and ccfDNA extraction methods. The results successfully demonstrated that spiking plasmid-derived material into plasma did not deleteriously interfere with endogenous ccfDNA recovery. The approach performed consistently across a range of commonly-used extraction protocols and was able to highlight differences in efficiency and variability between the methods, with the dPCR quantification assay performing with good repeatability (generally CV <5%). We conclude that initial findings demonstrate that this approach appears “fit for purpose” and spike-in recovery can be combined with other extraction QC metrics for monitoring the performance of a process over time, or in the context of external quality assessment.

Postirradiation temperature influences DSB repair and dicentric chromosome formation-potential impact for dicentric chromosome analysis in interlaboratory comparisons.

The objective was to investigate the influence of different pre-storage temperatures in the dicentric chromosome analysis (DCA) protocol (22°C vs. 37°C) by using γ-H2AX+53BP1 foci as a marker for deoxyribonucleic acid (DNA) double-strand break (DSB) damage induction and repair and the formation of dicentric chromosomes as a result of mis-repair. Repair of γ-H2AX+53BP1 DSB foci was absent in samples that were incubated for 2h at 22°C after exposure of 0.5 and 1.2Gy. When 0.5- and 1.2-Gy-exposed samples were incubated at 37°C for 2h, there was an average decline of 31 and 52% of DSB foci, respectively. This indicated that DNA repair occurred. There was a 27% decrease in dicentric chromosome yield at 1.2Gy and a 15% decrease at 3.5Gy after post-irradiation incubation for 2 h at 37°C relative to the observed dicentric frequencies at 22°C. Recommended to re-phase: our data suggested that there were more open DSBs after a 2-h incubation at 22°C, which contributed to more mis-repair and dicentric formation from the start of culture. Our findings are corroborated by publications showing that lesion interaction based on enzymatic activity is suppressed below 21°C. As such temperature variations can be a source of variation in DCA during interlaboratory comparison studies, we propose to establish a common guide for the standardisation of pre-culture conditions in cytogenetic dosimetry proficiency testing.

Quantitative and Qualitative Analyses of Mass Spectra of OEL Materials by Artificial Neural Network and Interface Evaluation: Results from a VAMAS Interlaboratory Study.

Quantitative analysis of binary mixtures of tris(2-phenylpyridinato)iridium(III) (Ir(ppy)3) and tris(8-hydroxyquinolinato)aluminum (Alq3) by using an artificial neural network (ANN) system to mass spectra was attempted based on the results of a VAMAS (Versailles Project on Advanced Materials and Standards) interlaboratory study (TW2 A31) to evaluate matrix-effect correction and to investigate interface determination. Monolayers of binary mixtures having different Ir(ppy)3 ratios (0, 0.25, 0.50, 0.75, and 1.00), and the multilayers containing these mixtures and pure samples were measured using time-of-flight secondary ion mass spectrometry (ToF-SIMS) with different primary ion beams, OrbiSIMS (SIMS with both Orbitrap and ToF mass spectrometers), laser desorption ionization (LDI), desorption/ionization induced by neutral clusters (DINeC), and X-ray photoelectron spectroscopy (XPS). The mass spectra were analyzed using a simple ANN with one hidden layer. The Ir(ppy)3 ratios of the unknown samples and the interfaces of the multilayers were predicted using the simple ANN system, even though the mass spectra of binary mixtures exhibited matrix effects. The Ir(ppy)3 ratios at the interfaces indicated by the simple ANN were consistent with the XPS results and the ToF-SIMS depth profiles. The simple ANN system not only provided quantitative information on unknown samples, but also indicated important mass peaks related to each molecule in the samples without a priori information. The important mass peaks indicated by the simple ANN depended on the ionization process. The simple ANN results of the spectra sets obtained by a softer ionization method, such as LDI and DINeC, suggested large ions such as trimers. From the first step of the investigation to build an ANN model for evaluating mixture samples influenced by matrix effects, it was indicated that the simple ANN method is useful for obtaining candidate mass peaks for identification and for assuming mixture conditions that are helpful for further analysis.

Inter-laboratory Study on the Modified Methods for Analyzing Bisphenol A Content for Migration Tests from Polycarbonate Food Apparatuses, Containers, and Packaging

An inter-laboratory study involving 24 laboratories was conducted to validate the modified analytical method for the migration solution of heptane for the determination of bisphenol A migrating from polycarbonate food processing materials. In this study, two concentrations of samples were blindly coded. Each laboratory determined the analyte (bisphenol A, phenol and p-tert-butylphenol) concentration in each sample according to the established protocol. The obtained values were analyzed statistically using internationally accepted guidelines. Horwitz ratios were calculated based on the reproducibility relative standard deviation (RSDR), which was estimated from the inter-laboratory study, and predicted RSDR, which was calculated using the Horwitz/Thompson equation. Horwitz ratios of the two samples ranged from 0.15 to 0.37 for the three compounds, meeting the performance criteria of less than 2 set by the Codex Alimentarius for analytical method approval. These results showed that this modified analytical method shows good performance as an analytical method for the migration solution of heptane.

Work function measurement by ultraviolet photoelectron spectroscopy: Versailles project on advanced materials and standards interlaboratory study

We present the results of an interlaboratory study on work function (WF) measurements by ultraviolet photoelectron spectroscopy (UPS) conducted under the auspices of the Versailles Project on Advanced Materials and Standards. Two samples, gold (Au) film deposited on a flat Si(100) and highly oriented pyrolytic graphite (HOPG), were distributed to six different laboratories. Prior to UPS measurements, the samples underwent common sample pre-cleaning procedures: wet treatment and Ar+-sputtering in a vacuum for Au, and mechanical peeling in air for HOPG. Instrumental settings are adjusted for energy-scale calibration and sample bias optimization. The average reference WF value (WFref) and its expanded uncertainty (Uref) were calculated from each dataset that participants provided. The results of the Au sample demonstrated 5.40 ± 0.13 eV after Ar+ sputtering in vacuum, while the HOPG sample showed 4.62 ± 0.16 eV after mechanical peeling-off. Even though the participants used slightly different sample bias voltages and sample cleaning methods with various instruments, the results demonstrate remarkable consistency. Their consistency among the laboratories for both samples with high and low WF values provides a basis for establishing a new international standard for UPS in the surface chemical analysis community.

Bayesian estimation in multivariate inter-laboratory studies with unknown covariance matrices

In the paper we present Bayesian inference procedures for the parameters of multivariate random effects model, which is used as a quantitative tool for performing multivariate key comparisons and multivariate inter-laboratory studies. The developed new approach does not require that the reported covariance matrices of participating laboratories are known and, as such, it can be used when they are estimated from the measurement results. The Bayesian inference procedures are based on samples generated from the derived posterior distribution when the Berger and Bernardo reference prior and the Jeffreys prior are assigned to the model parameter. Three numerical algorithms for the construction of Markov chains are provided and implemented in the CCAUV.V-K1 key comparisons. All three approaches yield similar Bayesian estimators with wider credible intervals when the Berger and Bernardo reference prior is used. Also, the Bayesian estimators for the elements of the inter-laboratory covariance matrix are larger under this prior than for the Jeffreys prior. Finally, the constructed joint credible sets for the components of the overall mean vector indicate the presence of linear dependence between them which cannot be captured when only univariate key comparisons are performed.

Development of a certified reference material for accurate determination of the leaching of Pb and Zn in solid waste.

Certified reference materials (CRMs) with high accuracy and traceability play a significant role in the calibration of equipment and validation of analytical methods. However, there is still a lack of suitable solid waste CRMs for quality assurance and quality control. Thus, a CRM (GBW(E)085538) was developed for accurate determination and reliable measurement of the leaching of Pb and Zn in solid waste according to the requirements of ISO 17034 and the recommendations of ISO Guide 35. This study describes the steps performed for the development of the CRM. These steps include material preparation, homogeneity, and stability during transport and storage, assignment of certified values, and their uncertainties. The material was dried, ground, sieved and well-mixed, and the final bulk material was bottled in 1kg portions. Analytical techniques like inductively coupled plasma-mass spectrometry (ICP-MS), inductively coupled plasma-optical emission spectrometry (ICP-OES), and flame atomic absorption spectrometry (AAS) have been used for the characterization of property values. Concurrently, an inter-laboratory comparison study involving 9 qualified laboratories was implemented to support the certification study. The certified values of Pb and Zn were (4.66 ± 0.21) mg/L and (2.95 ± 0.14) mg/L with 7-month stability.

Interlaboratory study: Testing reproducibility of solid biofuels component identification using reflected light microscopy

Considering global market trends and concerns about climate change and sustainability, increased biomass use for energy is expected to continue. As more diverse materials are being utilized to manufacture solid biomass fuels, it is critical to implement quality assessment methods to analyze these fuels thoroughly. One such method is reflected light microscopy (RLM), which has the potential to complement and enhance current standard testing, leading to improving fuel quality assessment and, ultimately, preventing avoidable air pollution.An interlaboratory study (ILS) was conducted to test the reproducibility of biomass fuels component identification using a reflected light microscopy technique. The exercise was conducted on thirty photomicrographs showing biomass and various undesired components (like plastics or mineral matter), which were purposely added (by the ILS organizers) to contaminate wood pellets and charcoal-based grilling fuels.Forty-six participants had various levels of difficulty identifying the marked components, and as a result, the percentage of correct answers ranged from 52.2 to 94.4%. Among the most difficult components to distinguish were petroleum products and inorganic matter. Various reasons led to the misidentification, including insufficient morphological descriptions of the components provided to participants, ambiguities of the nomenclature, limitations of the analytical and exercise method, and insufficient experience of the participants.Overall, the results indicate that RLM has the potential to enhance the quality assessment of biomass fuels. However, they also demonstrate that the petrographic classification used in this exercise requires further refinement before it can be standardized. While a new simplified classification of solid biomass fuels components was created as an outcome of this study, future research is necessary to refine the nomenclature, develop a microscopic morphological description of the components, and verify the accuracy of component identification with a follow-up ILS.

Interlaboratory study on lipid oxidation during accelerated storage trials with rapeseed and sunflower oil analyzed by conjugated dienes as primary oxidation products

AbstractAccelerated storage tests are frequently used to assess the oxidative stability of foods and related systems due to its reproducibility. Various methods and experimental conditions are used to measure lipid oxidation. Differences between laboratories make it necessary to determine the repeatability and reproducibility of oxidation tests performed under the same conditions. The objective of the present interlaboratory study was to evaluate the outcome of a storage test for two different bulk oils, sunflower oil (SFO) and rapeseed oil (RSO), during a period of 9 weeks at 20°C, 30°C, 40°C, and 60°C. Sixteen laboratories were provided with bottled oils and conducted the storage tests according to a detailed protocol. Lipid oxidation was monitored by the formation of conjugated dienes (CD) and the activation energy (Ea) was determined for comparative purposes and statistically evaluated. An increase in CD formation was observed for both oils when the storage temperature was increased in all laboratories. The Ea,1 ranged from 47.9 to 73.3 kJ mol−1 in RSO and from 27.8 to 62.6 kJ mol−1 in SFO, with average values of 58.2 and 46.8 kJ mol−1, respectively. The reproducibility coefficients were 10.9% and 18.2% for RSO and SFO, respectively.Practical applications: In order to compare results on oxidative stability of foods derived from different studies, the reproducibility of storage tests and methods employed to evaluate the oxidation level should be considered. This study provides fundamental data on the reproducibility of lipid oxidation under accelerated storage conditions and defines important parameters to be considered for the conduction of experiments.

Evaluation of a high-throughput H295R homogenous time resolved fluorescence assay for androgen and estrogen steroidogenesis screening

The H295R test guideline assay evaluates the effect of test substances on synthesis of 17β-estradiol (E2) and testosterone (T). The objective of this study was to leverage commercial immunoassay technology to develop a more efficient H295R assay to measure E2 and T levels in 384-well format. The resulting Homogenous Time Resolved Fluorescence assay platform (H295R-HTRF) was evaluated against a training set of 36 chemicals derived from the OECD inter-laboratory validation study, EPA guideline 890.1200 aromatase assay, and azole fungicides active in the HT-H295R assay. Quality control performance criteria were met for all conditions except E2 synthesis inhibition where low basal hormone synthesis was observed. Five proficiency chemicals were active for both the E2 and T endpoints, consistent with guideline classifications. Of the nine OECD core reference chemicals, 9/9 were concordant with outcomes for E2 and 7/9 for T. Likewise, 9/13 and 11/13 OECD supplemental chemicals were concordant with anticipated effects for E2 and T, respectively. Of the 10 azole fungicides screened, 7/10 for E2 and 8/10 for T exhibited concordant outcomes for inhibition. Generally, all active chemicals in the training set demonstrated equivalent or greater potency in the H295R-HTRF assay, supporting the sensitivity of the platform. The adaptation of HTRF technology to the H295R model provides an efficient way to evaluate E2 and T modulators in accordance with guideline specifications.

Standardizing In Vitro β-Lactam Antibiotic Allergy Testing with Synthetic IgE.

The global prevalence of β-lactam allergy poses a major challenge in administering first-line antibiotics, such as penicillins, to a significant portion of the population. The lack of β-lactam IgE antibody pools with defined selectivity hampers the standardization and validation of in vitro assays for β-lactam allergy testing. To address this limitation, this study introduces a synthetic IgE specific to β-lactam antibiotics as a valuable tool for drug allergy research and diagnostic tests. Using phage display technology, we constructed a library of human single-chain antibody fragments (scFv) to target the primary determinant of amoxicillin, a widely used β-lactam antibiotic. Subsequently, we produced a complete human synthetic IgE molecule using the highly efficient baculovirus expression vector system. This synthetic IgE molecule served as a standard in an in vitro chemiluminescence immunoassay for β-lactam antibiotic allergy testing. Our results demonstrated a detection limit of 0.05 IU/mL (0.63 pM), excellent specificity (100%), and a four-fold higher clinical sensitivity (73%) compared to the in vitro reference assay when testing a cohort of 150 serum samples. These findings have significant implications for reliable interlaboratory comparison studies, accurate labeling of allergic patients, and combating the global public health threat of antimicrobial resistance. Furthermore, by serving as a valuable trueness control material, the synthetic IgE facilitates the standardization of diagnostic tests for β-lactam allergy and demonstrates the potential of utilizing this synthetic strategy as a promising approach for generating reference materials in drug allergy research and diagnostics.

Analysis of Selenium in Fish Tissue: An Interlaboratory Study on Weight Constraints.

Environmental monitoring programs that target fish tissues for selenium (Se) analysis present unique sampling and analytical challenges. Se monitoring programs ideally focus on egg/ovary sampling but frequently sample multiple tissues with varying lipid content, often target small-bodied fish species due to their small home ranges, and require reporting in units of dry weight. Additionally, there is a growing impetus for non-lethal tissue sampling in fish monitoring. As a result, Se monitoring programs often generate low-weight tissue samples of varying lipid content, which challenges analytical laboratories to quantify tissue selenium concentrations accurately, precisely, and at desired detection limits. The objective of this study was to stress-test some conventional analytical techniques used by commercial laboratories in terms of their ability to maintain data quality objectives in the face of sample weight constraints. Four laboratories analyzed blind a suite of identical samples, and data were compared against a priori data quality objectives for accuracy, precision, and sensitivity. Data quality tended to decrease with decreasing sample weight, particularly when samples were less than the minimum weights requested by the participating laboratories; however, effects of sample weight on data quality were not consistent among laboratories or tissue types. This study has implications for accurately describing regulatory compliance in selenium monitoring programs, highlighting some important considerations for achieving high data quality from low-weight samples.

Performance Characteristics of Mass Spectrometry-Based Analytical Procedures for Quantitation of Nitrosamines in Pharmaceuticals: Insights from an Inter-laboratory Study

With the discovery of carcinogenic nitrosamine impurities in pharmaceuticals in 2018 and subsequent regulatory requirements for risk assessment for nitrosamine formation during pharmaceutical manufacturing processes, storage or from contaminated supply chains, effective testing of nitrosamines has become essential to ensure the quality of drug substances and products. Mass spectrometry has been widely applied to detect and quantify trace amounts of nitrosamines in pharmaceuticals. As part of an effort by regulatory authorities to assess the measurement variation in the determination of nitrosamines, an inter-laboratory study was performed by the laboratories from six regulatory agencies with each of the participants using their own analytical procedures to determine the amounts of nitrosamines in a set of identical samples. The results demonstrated that accurate and precise quantitation of trace level nitrosamines can be achieved across multiple analytical procedures and provided insight into the performance characteristics of mass spectrometry-based analytical procedures in terms of accuracy, repeatability and reproducibility.