Interlaboratory Comparison Research Articles

Contaminants of emerging concern in urine: a review of analytical methods for determining diisocyanates, benzotriazoles, benzothiazoles, 4-methylbenzylidene camphor, isothiazolinones, fragrances, and non-phthalate plasticizers.

Human biomonitoring (HBM)frameworks assess human exposure to hazardous chemicals. In this review, we discuss and summarize sample preparation procedures and analytical methodology for six groups of chemicals of emerging concern (CECs), namely diisocyanates, benzotriazoles, benzothiazoles, 4-methylbenzylidene camphor, isothiazolinones, fragrances, and non-phthalate plasticizers, which are increasingly detected in urine, however, are not yet widely included in HBM schemes, despite posing a risk to human health. The sample preparation procedures depend largely on the chemical group; however, solid-phase extraction (SPE) is most often used due to the minimized sample handling, lower sample volume, and generally achieving lower limits of quantification (LOQs) compared to other extraction techniques. In terms of sample analysis, LC-based methods generally achieve lower limits of quantification (LOQs) compared to GC-based methods for the selected six groups of chemicals owing to their broader chemical coverage. In conclusion, since these chemicals are expected to be more frequently included in future HBM studies, it becomes evident that there is a pressing need for rigorous quality assurance programs to ensure better comparability of data. These programs should include the reporting of measurement uncertainty and facilitate inter-laboratory comparisons among the reporting laboratories. In addition, high-resolution mass spectrometry should be more commonly employed to enhance the specificity and selectivity of the applied analytical methodology since it is underrepresented in HBM. Furthermore, due to the scarcity of data on the levels of these CECs in urine, large population HBM studies are necessary to gain a deeper understanding of the associated risks.

Development and validation of a multianalyte method for quantification of isoxazolines in animal-derived matrix samples using SPE-HPLC–MS/MS

Isoxazoline drugs, including afoxolaner, fluralaner, lotilaner, and sarolaner, are widely used in veterinary medicine. However, the lack of available analytical methods has made regulatory monitoring of these drugs difficult. Therefore, in this study, we developed an optimized solid phase extraction process using hydrophilic–lipophilic cartridges, and subsequently analyzed the extracts using liquid chromatography–tandem mass spectrometry under optimized conditions. The detection limits for the four isoxazolines were 5.0 μg/kg, while the recoveries in six animal-derived matrices were 71.1–109.2 %, with intra-day and inter-day relative standard deviations below 11.9 % and 11.7 % respectively. Furthermore, an inter-laboratory comparison demonstrated that this method had good recovery (60.3–112.9 %) and acceptable precision (< 11.3 %). Additionally, the developed method exhibited excellent linearity, accuracy, precision, sensitivity, measurement uncertainty and robustness for isoxazoline residue determination in animal-derived samples. It was also successfully applied to determine incurred isoxazoline residues in medicated hens.

Second intercomparison on electron paramagnetic resonance (EPR) retrospective dosimetry in Korea using hydroxyapatite

The Korea retrospective dosimetry (KREDOS)–electron paramagnetic resonance (EPR) group undertook an intercomparison investigation utilizing hydroxyapatite. This analysis involved four institutions: the Korea Institute of Radiological and Medical Sciences, Dongnam Institute of Radiological and Medical Sciences, Korean Association for Radiation Application, and Radiation Health Institute of Korea Hydro & Nuclear Power. Following the irradiation of the hydroxyapatite sample, the recorded build-up was analyzed. To validate the reliability of the EPR dosimetry findings and enhance its operational performance, a hydroxyapatite dose–response curve was plotted and dosimetry was performed for a blind sample. The proficiency of each laboratory was assessed by employing an interlaboratory comparison methodology. This involved a comparative analysis of the measurement results by calculating the relative bias, z-score, and En value. The results submitted by the participating laboratories demonstrated satisfactory ratings for doses of 1.006, 3.999, and 6.993 Gy. Following the second intercomparison, efforts to optimize their hydroxyapatite-EPR dosimetry systems are underway in the participating laboratories. The current assessment of hydroxyapatite dose yielded the foundational data required to establish the parameters of dental dosimetry. In future, the third intercomparison experiment will be conducted for exploring other materials.

VAMAS TWA2 interlaboratory comparison: Surface analysis of TiO2 nanoparticles using ToF-SIMS

Due to the extremely high specific surface area of nanoparticles and corresponding potential for adsorption, the results of surface analysis can be highly dependent on the history of the particles, particularly regarding sample preparation and storage. The sample preparation method has, therefore, the potential to have a significant influence on the results. This report describes an interlaboratory comparison (ILC) with the aim of assessing which sample preparation methods for ToF-SIMS analysis of nanoparticles provided the most intra- and interlaboratory consistency and the least amount of sample contamination. The BAM reference material BAM-P110 (TiO2 nanoparticles with a mean Feret diameter of 19 nm) was used as a sample representing typical nanoparticles. A total of 11 participants returned ToF-SIMS data, in positive and (optionally) negative polarity, using sample preparation methods of “stick-and-go” as well as optionally “drop-dry” and “spin-coat.” The results showed that the largest sources of variation within the entire data set were caused by adventitious hydrocarbon contamination or insufficient sample coverage, with the spin-coating protocol applied in this ILC showing a tendency toward insufficient sample coverage; the sample preparation method or the participant had a lesser influence on results.

Development and validation of UV spectrophotometric method for estimation of naringenin in phytosomal formulation: interlaboratory comparison, capability, and statistical analysis.

The goal of the current work was to establish a simple, reproducible, and reliable UV spectrophotometric method for determining naringenin in phytosomal formulations. The solvent methanol was optimized and spectrophotometric analysis was carried out at 289nm. The proposed method was also validated for linearity, specificity, accuracy, precision, ruggedness, and robustness in accordance with the International Council for Harmonisation (ICH). With a correlation coefficient of 0.9982, the concentration of naringenin in the range of 2-14μg/ml follows Lambert-Beer rule. The accuracy ranged between 99.33 and 99.75%. The predicted percent recovery was found to be 99.48 ± 0.41. It was found that the limits of detection (LOD) and quantification were 0.54μg/ml and 1.66μg/ml, respectively. The normality of the data is accepted by the Shapiro-Wilk test (P = 0.9065) and Shapiro-Francia test (W = 0.9866). On the Bland-Altman plot, an acceptable repeatability coefficient was found. The remarkable inter-laboratory repeatability was proved by the Youden plot, which was also utilized to spot random and total errors. Levey-Jennings charts and other control diagrams have demonstrated that the method is statistically controlled. Greater values of Cp (1.03) and Cpk (0.83) were seen in the capability analysis, indicating that the method could analyze the samples reliably and consistently with minimum variation. The validation report demonstrated that the proposed method was appropriate for naringenin detection and analysis in phytosomal formulations, indicating that it can be employed for routine laboratory analysis as well.

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.

Stable cerium isotope analysis of geological materials by MC-ICP-MS

We report stable cerium (Ce) isotopic compositions of terrestrial rocks and investigate Ce isotopic fractionation during column chemistry in this study. Cerium was separated from matrix elements by a single-stage extraction technique using Eichrom DGA resin. Ce isotope ratios were measured using a Thermo Scientific Neptune Plus MC-ICP-MS employing a sample–standard combined with a Sm-doping method. The data accuracy and precision of Ce isotope analyses were rigorously examined by two different laboratories. The δ142Ce values of mono-elemental Ce standards (JMC304 and CDUT-Ce) relative to NIST SRM 3110 solution were − 0.005 ± 0.042‰ (2SD, N = 9) and 0.118 ± 0.033‰ (2SD, N = 6), respectively. The δ142Ce of the manganese nodule (NOD-P-1) measured in two laboratories were 0.177 ± 0.035‰ (2SD, N = 7) and 0.172 ± 0.034‰ (2SD, N = 8), respectively; NOD-A-1 were 0.116 ± 0.028‰ (2SD, N = 8) and 0.104 ± 0.028‰ (2SD, N = 9), respectively. The offset between these two manganese nodules could be possibly related with their unique diagenetic environments. The δ142Ce of two USGS standards diabase W-2a was −0.036 ± 0.046‰ (2SD, N = 3), basalt BHVO-2 was −0.019 ± 0.036‰ (2SD, N = 4). Ce isotopic compositions of three Chinese reference standards granite gneiss GBW07121, diabase GBW07123, and stream sediment GBW07301a were 0.039 ± 0.033‰ (2SD, N = 5), 0.068 ± 0.027‰ (2SD, N = 5) and 0.046 ± 0.015‰ (2SD, N = 3), respectively. The reported data will be helpful for quality assurance and inter-laboratory comparison for high-precision Ce isotopic studies.Full recovery is important to achieve high precision and high accuracy data for metal isotopes. To understand Ce isotope behavior during column separation, an experiment with different Ce cuts was conducted. The δ142Ce of JMC304 and NIST SRM 3110 in five different Ce subcuts varied from 0.047 ± 0.020‰ (2SD, N = 3; 0–25% cut) to −0.029 ± 0.047‰ (2SD, N = 5; 45–100% cut), and 0.058 ± 0.047‰ (2SD, N = 4; 0–11% cut) to −0.022 ± 0.033‰ (2SD, N = 4; 32–100% cut), respectively. δ142Ce of these subcuts showed small ranges, but isotopic fractionation of Ce did occur during column chemistry and light isotopes are preferentially retained in the DGA resin.

Synthetic Witherite for Standardisation of Clumped Isotope (Δ47) Measurements

Carbonate clumped isotope, quantified by Δ47 value, has wide application potential in Earth science. A recently proposed carbonate standardisation scheme based on community‐available reference materials (i.e., ETH‐1–4) has proven to improve interlaboratory comparability in Δ47 measurement. However, the shortage of these reference materials may be problematic in future; therefore, developing traceable and supplementary in‐house reference materials may become necessary, especially when supplies run out. Here, we describe a method of producing synthetic witherite carbonates with variable bulk isotopic compositions and clumped isotope ordering states, for which Δ47 values were determined together with ETH carbonate reference materials. Results indicate that the witherite carbonates allow effective corrections for instrumental linearity and scale variations, improving long‐term reproducibility. Additionally, by normalising witherite Δ47 values to agreed ETH carbonate values on the Intercarb‐Carbon Dioxide Equilibrium Scale, the witherite reference materials can be used to determine Δ47 values without using equilibrated gases and reduce the consumption of ETH carbonates.

Development of a novel certified reference material for the determination of polycyclic aromatic hydrocarbons (PAHs) in whey protein powder

Matrix-based certified reference materials (CRMs) play a central role in the analysis of food contaminants for ensuring measurement accuracy and comparability, as they exhibit the same matrix effects during sample preparation and measurement as the food sample under investigation. However, the availability of such CRMs is still limited. This is also true for matrix CRMs containing polycyclic aromatic hydrocarbons (PAHs), for which maximum levels in food are set in the EU by the Commission Regulation (EU) 2023/915 and in Switzerland by the regulation SR 817.022.15. Therefore, a whey protein powder–based certified reference material (WP-CBR001) was developed according to the requirements of ISO 17034 and the recommendations of ISO Guide 35:2017 containing the four PAHs benz[a]anthracene (BaA), benzo[a]pyrene (BaP), benzo[b]fluoranthene (BbF), and chrysene (Chr). We show that the choice of solvent is of crucial importance to extract the PAHs completely from this matrix. Only polar and protic solvents such as methanol or water provided access for complete extraction of the PAHs. In contrast, nonpolar and polar aprotic solvents, such as n-hexane or ethyl acetate, exhibited only very low extraction efficiencies below 20%. The certified mass fractions and expanded uncertainties (k = 2) were (3.17 ± 0.32) µg/kg BaA, (4.18 ± 0.48) µg/kg BaP, (4.73 ± 0.49) µg/kg BbF, and (2.85 ± 0.33) µg/kg Chr. These values were verified by an interlaboratory comparison study and by the gravimetric mass fractions obtained from production data.Graphical abstract

Characterisation of Conventional 87Sr/86Sr Isotope Ratios in Cement, Limestone and Slate Reference Materials Based on an Interlaboratory Comparison Study

An interlaboratory comparison (ILC) was organised to characterise 87Sr/86Sr isotope ratios in geological and industrial reference materials by applying the so‐called conventional method for determining 87Sr/86Sr isotope ratios. Four cements (VDZ 100a, VDZ 200a, VDZ 300a, IAG OPC‐1), one limestone (IAG CGL ML‐3) and one slate (IAG OU‐6) reference materials were selected, covering a wide range of naturally occurring Sr isotopic signatures. Thirteen laboratories received aliquots of these six reference materials together with a detailed technical protocol. The consensus values for the six reference materials and their associated measurement uncertainties were obtained by applying a Gaussian, linear mixed effects model fitted to all the measurement results. By combining the consensus values and their uncertainties with an uncertainty contribution for potential heterogeneity, reference values ranging from 0.708134 mol mol‐1 to 0.729778 mol mol‐1 were obtained with relative expanded uncertainties of ≤ 0.007 %. This study represents an ILC on conventional 87Sr/86Sr isotope ratios, within which metrological principles were considered and the compatibility of measurement results obtained by MC‐ICP‐MS and by MC‐TIMS is demonstrated. The materials characterised in this study can be used as reference materials for validation and quality control purposes and to estimate measurement uncertainties in conventional 87Sr/86Sr isotope ratio measurement.

Exploratory Acoustic Investigation of Customizable 3D-Printed Hybrid Acoustic Materials (HAMs) through Interlaboratory Impedance Tube Measurements

Acoustic materials are widely used for improving interior acoustics based on their sound absorptive or sound diffusive properties. However, common acoustic materials only offer limited options for customizable geometrical features, performance, and aesthetics. This paper focuses on the sound absorption performance of highly customizable 3D-printed Hybrid Acoustic Materials (HAMs) by means of parametric stepped thickness, which is used for sound absorption and diffusion. HAMs were parametrically designed and produced using computational design, 3D-printing technology, and feedstock material with adjustable porosity, allowing for the advanced control of acoustic performance through geometry-related sound absorbing/diffusing strategies. The proposed design methodology paves the way to a customizable large-scale cumulative acoustic performance by varying the parametric stepped thickness. The present study explores the challenges posed by the testing of the sound absorption performance of HAMs in an impedance tube. The representativeness of the test samples (i.e., cylindrical sections) with respect to the original (i.e., rectangular) panel samples is contextually limited by the respective impedance tube’s geometrical features (i.e., cylindrical cross-section) and dimensional requirements (i.e., diameter size). To this aim, an interlaboratory comparison was carried out by testing the normal incidence sound absorption of ten samples in two independent laboratories with two different impedance tubes. The results obtained demonstrate a good level of agreement, with HAMs performing better at lower frequencies than expected and behaving like Helmholtz absorbers, as well as demonstrating a frequency shift pattern related to superficial geometric features.

On modelling of artefact instability in interlaboratory comparisons

Key comparisons are at the core of metrology and support the international equivalence of measurement standards. Typical key comparison setups involve travelling artefacts which are transferred between the participants of a study. After each participating laboratory performs its measurements of the artefacts, a subsequent analysis reveals the degree of equivalence between the participants. For this analysis stage, the stability of the artefacts plays a crucial role, and violations of the stability need to be taken into account to allow for a meaningful comparison. In this work, we present several mathematical models for a treatment of non-negligible artefact instability effects in bilateral comparisons. We highlight the underlying model assumptions and derive analytical formulae for the estimate and standard uncertainty of the instability effect. Moreover, we derive the bilateral degree of equivalence by applying the models in a treatment essentially based on the GUM (JCGM-100). Our considerations conclude with numerical experiments using data from a bilateral comparison on illuminance and from a recent CCM key comparison of kilogram realisations.

LC-MS/MS analysis of erythrocyte phosphatidylethanol in haematocrit-corrected whole blood versus isolated erythrocytes: Results of an inter-laboratory comparison.

Phosphatidylethanol (PEth) is a non-oxidative metabolite of alcohol (ethanol), which is a sensitive and specific indicator of historic ethanol consumption. Although PEth production from ethanol is catalysed by the ubiquitous enzyme phospholipase D, it resides mainly within the erythrocyte compartment of the blood. PEth analysis has been reported in different preparations of whole blood, representing one of the barriers of inter-laboratory comparisons. We previously reported that expressing PEth concentrations in terms of blood erythrocyte content is more sensitive than whole blood volume, and haematocrit-corrected liquid whole blood calculations of erythrocyte PEth and isolated erythrocyte PEth concentrations are comparable when assayed under identical analytical conditions. Acceptance of a clinical diagnostic assay by accreditation bodies requires proficiency testing with a third-party analytical facility. To explore different blood preparations within the same inter-laboratory program, 60 matched isolated erythrocyte or liquid whole blood specimens were tested at three laboratories. Laboratories measured PEth by liquid chromatography-tandem mass spectrometry (LC-MS/MS), two using isolated erythrocytes, while the third used liquid whole blood, which underwent haematocrit correction before comparison with isolated erythrocyte PEth concentrations. There was acceptable consensus (87%) among laboratories to detect PEth around a cut-off of 35 μg/L of erythrocytes. Each laboratory correlated well with the group average PEth concentration (R > 0.98) for each specimen above the cut-off. Differences were observed between laboratories in bias, which did not affect comparable sensitivity at the selected cut-off. This work demonstrates the feasibility of an inter-laboratory comparison for erythrocyte PEth analysis across different LC-MS/MS methodologies and different blood preparations.

Reproducibility of the wet part of the soil water retention curve: a European interlaboratory comparison

Abstract. The soil water retention curve (SWRC) is a key soil property required for predicting basic hydrological processes. The SWRC is often obtained in the laboratory with non-harmonized methods. Moreover, procedures associated with each method are not standardized. This can induce a lack of reproducibility between laboratories using different methods and procedures or using the same methods with different procedures. The goal of this study was to estimate the inter- and intralaboratory variability of the measurement of the wet part (from 10 to 300 hPa) of the SWRC. An interlaboratory comparison was carried out between 14 laboratories, using artificially constructed, porous reference samples that were transferred between laboratories according to a statistical design. The retention measurements were modelled by a series of linear mixed models using a Bayesian approach. This allowed the detection of sample-to-sample variability, interlaboratory variability, intralaboratory variability and the effects of sample changes between measurements. The greatest portion of the differences in the measurement of SWRCs was due to interlaboratory variability. The intralaboratory variability was highly variable depending on the laboratory. Some laboratories successfully reproduced the same SWRC on the same sample, while others did not. The mean intralaboratory variability over all laboratories was smaller than the mean interlaboratory variability. A possible explanation for these results is that all laboratories used slightly different methods and procedures. We believe that this result may be of great importance regarding the quality of SWRC databases built by pooling SWRCs obtained in different laboratories. The quality of pedotransfer functions or maps that might be derived is probably hampered by this inter- and intralaboratory variability. The way forward is that measurement procedures of the SWRC need to be harmonized and standardized.

Report of RILEM TC 281-CCC: effect of loading on the carbonation performance of concrete with supplementary cementitious materials — an interlaboratory comparison of different test methods and related observations

Report of RILEM TC 281-CCC: effect of loading on the carbonation performance of concrete with supplementary cementitious materials — an interlaboratory comparison of different test methods and related observations

Developments of interlaboratory comparisons on pressure measurements in the Philippines

The National Metrology Laboratory of the Philippines, Industrial Technology Development Institute under the Department of Science and Technology (ITDI-DOST) offered first of its kind interlaboratory comparison in pressure measurement in the country following a demand survey identifying the gaps in proving the competency of local calibration laboratories. This paper presents the development in implementing the two interlaboratory comparisons in the Philippines with six years interval using the same pressure artefact. With its many objectives, the program also aimed to provide these laboratories access to proficiency testing (PT) to comply with the ISO/IEC 17025 requirements. Comparatively, while both are considered successfully implemented, the improved awareness and commitment to quality of the participants and the enhanced competency of the pilot laboratory in implementing such activity are a few of the enumerated factors instigating the increase in the number of participants as well as those obtaining satisfactory results in the latter PT. The interlaboratory comparison schemes offered aimed at sustaining the demands of metrology stakeholders and continuously develop this service to support further progress in the calibration and measurement capabilities of local laboratories in the country.

Inter-laboratory comparison of plant volatile analyses in the light of intra-specific chemodiversity

IntroductionAssessing intraspecific variation in plant volatile organic compounds (VOCs) involves pitfalls that may bias biological interpretation, particularly when several laboratories collaborate on joint projects. Comparative, inter-laboratory ring trials can inform on the reproducibility of such analyses.ObjectivesIn a ring trial involving five laboratories, we investigated the reproducibility of VOC collections with polydimethylsiloxane (PDMS) and analyses by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). As model plant we used Tanacetum vulgare, which shows a remarkable diversity in terpenoids, forming so-called chemotypes. We performed our ring-trial with two chemotypes to examine the sources of technical variation in plant VOC measurements during pre-analytical, analytical, and post-analytical steps.MethodsMonoclonal root cuttings were generated in one laboratory and distributed to five laboratories, in which plants were grown under laboratory-specific conditions. VOCs were collected on PDMS tubes from all plants before and after a jasmonic acid (JA) treatment. Thereafter, each laboratory (donors) sent a subset of tubes to four of the other laboratories (recipients), which performed TD-GC-MS with their own established procedures.ResultsChemotype-specific differences in VOC profiles were detected but with an overall high variation both across donor and recipient laboratories. JA-induced changes in VOC profiles were not reproducible. Laboratory-specific growth conditions led to phenotypic variation that affected the resulting VOC profiles.ConclusionOur ring trial shows that despite large efforts to standardise each VOC measurement step, the outcomes differed both qualitatively and quantitatively. Our results reveal sources of variation in plant VOC research and may help to avoid systematic errors in similar experiments.

A Different Perspective on the Characterization of a New Degradation Product of Flibanserin with HPLC-DAD-ESI-IT-TOF-MSn and its Pharmaceutical Formulation Analysis with Inter-Laboratory Comparison.

Flibanserin (FLB) was firstly synthesized as an antidepressant drug; however, due to its enhancing effects on sexual activity, it was approved for treatment of hypoactive sexual desire disorder in women in 2015. The aim of this study was to develop a new and fully validated HPLC method for analysis of FLB in pharmaceutical formulations besides its degradation products, and identification of possible formation mechanisms by using HPLC-DAD-ESI-IT-TOF-MSn. The HPLC separation was achieved in an Supelco Ascentis® Express series phenyl hexyl column (100 × 4.6 mm, ID 2.7µm). The mobile phase was acetonitrile-ammonium acetate solution (50:50, v/v, 10 mM, pH 5.4) mixture, which was pumped at the rate of 0.5 mL/min. Chromatography, detection and structural identification was performed by using LCMS-IT-TOF instrument (Shimadzu, Japan). 1-(2-(4-(3-hydroxy-5-(trifluoromethyl)phenyl)piperazine-1-yl)ethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one is proposed as a novel degradation product, with a mass of 407.1695, and a formula of C20H21F3N4O2 with a margin of error about 0.001 ppm. The developed method is applicable with 98% accuracy within 2.5-50.0 µg/mL range. The LOD and LOQ was about 500 ng/mL and 1.50 µg/mL, respectively. The transferability and variation between laboratories were tested by inter-laboratory comparison and evaluated with one-way analysis of variance. A novel FLB degradation product, which was produced under oxidative forced degradation condition was observed and identified for the first time; in addition, the formation kinetics of the degradation product, besides decomposition of FLB was studied. Furthermore, an inter-laboratory comparison was carried out and application of the proposed method on pseudo Addyi® sample was tested using both instrument configurations. A novel stability indicating assay method was developed and fully validated according to ICH (Q2)R1 for the analysis of FLB in the pharmaceutical preparations. A new degradation product was identified in the oxidative forced degradation condition and characterized using HPLC-DAD-ESI-IT-TOF-MS3. Moreover, the possible mechanism and the formation kinetic of the degradation product were revealed. In addition, the developed method was transferred to another LC-PDA instrument for inter-laboratory comparison. Finally, the current method was applied to pseudo formulation of Addy® in both instruments and ANOVA was applied for evaluation.

Calcium isotopic composition of widely available biological reference materials using collision cell (CC)-MC-ICP-MS

BackgroundThe application of isotopes of metals in medical science (isotope metallomics) has shown significant growth in the last few years, specifically with respect to the study of metal cycles in the body and/or their use as diagnostic tools for diseases that affect metal homeostasis. Given the great potential for Ca stable isotopes to identify changes in Ca metabolism and bone metabolism, there have been major applications of Ca metallomics—and isotope metallomics. However, reliable and high precision Ca isotopic analysis is challenging considering the limited Ca amounts in some soft tissues compared to e.g., bones and the related interference effect during measurement. Furthermore, there is a lack of Ca isotopic data in widely available biological reference materials with various matrices. MethodThe development of collision-cell multi-collection inductively-coupled-plasma mass-spectrometers (CC-MC-ICP-MS), such as the Nu Instrument Sapphire, has revolutionized Ca isotope analysis, improving the sensitivity by over a factor 10 compared to older generation instruments, and more readily overcoming isobaric interferences. In this study, we report the first set of high precision Ca isotopic data for several widely available biological reference materials, spanning both land and sea animals, as well as various bodily organs (muscle, kidney, liver). ResultResults indicate that animals are globally enriched in the lighter isotopes compared to their living environment, and that Ca isotopes are fractionated by more than 1.5 ‰ between organs (e.g., in bovine), further highlighting that Ca isotopes could be used to study Ca cycles within the body. ConclusionThese new data—and reference materials—could be used for future interlaboratory comparisons.

Production and certification of BOTS-1: bovine muscle-certified reference material for incurred veterinary drug residues.

A freeze-dried bovine muscle-certified reference material (CRM), known as BOTS-1 (DOI: https://doi.org/10.4224/crm.2018.bots-1 ), containing incurred residues of commonly used veterinary drugs was produced and certified for the mass fraction of eight veterinary drug residues. Value assignment was carried out using liquid chromatography tandem mass spectrometry (LC-MS/MS) methods in conjunction with isotope dilution and standard addition approaches involving stable isotope internal standards. Data from the National Research Council of Canada (NRC), Canadian Food Inspection Agency (CFIA), United States Department of Agriculture (USDA), and the Federal Office of Consumer Protection and Food Safety in Germany (BVL) were used for value assignment. Results for two drug residues were also obtained through an international inter-laboratory comparison CCQM-K141/P178 organized under the auspices of the International Bureau of Weights and Measures (BIPM). Quantitative NMR (1H-qNMR) was used to characterize primary standards of all veterinary drugs certified. The certified mass fractions of the veterinary drug residues were 490 ± 100µg/kg for chlorpromazine, 44 ± 4.4µg/kg for ciprofloxacin, 3.3 ± 1.4µg/kg for clenbuterol, 9.5 ± 0.8µg/kg for dexamethasone, 57 ± 4.8µg/kg for enrofloxacin, 3.0 ± 0.4µg/kg for meloxicam, 12.4 ± 1.2µg/kg for ractopamine, and 2290 ± 120µg/kg for sulfadiazine with expanded uncertainties quoted (95% confidence) which include the effects due to between-bottle inhomogeneity, instability during long-term storage and transportation, and characterization.