The implementation of ion mobility spectrometry (IMS) in liquid chromatography-high-resolution mass spectrometry (LC-HRMS) workflows has become a valuable tool for improving compound annotation in metabolomics analyses by increasing peak capacity and by adding a new molecular descriptor, the collision cross section (CCS). Although some studies reported high repeatability and reproducibility of CCS determination and only few studies reported good interplatform agreement for small molecules, standardized protocols are still missing due to the lack of reference CCS values and reference materials. We present a comparison of CCS values of approximatively one hundred lipid species either commercially available or extracted from human plasma. We used three different commercial ion mobility technologies from different laboratories, drift tube IMS (DTIMS), travelling wave IMS (TWIMS) and trapped IMS (TIMS), to evaluate both instrument repeatability and interlaboratory reproducibility. We showed that CCS discrepancies of 0.3% (average) could occur depending on the data processing software tools. Moreover, eleven CCS calibrants were evaluated yielding mean RSD below 2% for eight calibrants, ESI Low concentration tuning mix (Tune Mix) showing the lowest RSD (< 0.5%) in both ion modes. Tune Mix calibrated CCS from the three different IMS instruments proved to be well correlated and highly reproducible (R2 > 0.995 and mean RSD ≤ 1%). More than 90% of the lipid CCS had deviations of less than 1%, demonstrating high comparability between techniques, and the possibility to use the CCS as molecular descriptor. We highlighted the need of standardized procedures for calibration, data acquisition, and data processing. This work demonstrates that using harmonized analytical conditions are required for interplatform reproducibility for CCS determination of human plasma lipids.

External quality assessment programs (EQAP) for molecular haematology generally only assess the analytical phase of laboratory testing or provide limited evaluation of post-analytical components. We incorporated comprehensive post-analytical evaluation into an existing national inter-laboratory sample exchange program for molecular haematology due to the increasing complexity of diagnostic molecular testing and interpretation. We report key findings from four years of longitudinal data using this approach. Eighteen participating laboratories enrolled in an annual reciprocal sample exchange program from 2019-2022, which covered conventional and next-generation sequencing (NGS) assays. Participants submitted results on their laboratory information system-generated reports which then underwent central review. Reports were assessed according to consensus values and relevant national and international reporting standards and guidelines. A total of 680 reports were received. Laboratories had high concordance in the analytical phase of testing, with incorrect variant detection observed in a total of six of 680 (0.9%) reports. In contrast, post-analytical concordance was much lower, with at least one discordance observed in 28.9-57.6% of all conventional reports and 33.3-100% NGS reports. The most frequent post-analytical discordances were: (1) not including key technical information on reports (total 41.9% conventional, 47.2% NGS); (2) not using standard gene and variant nomenclature (total 28.2% conventional, 25.6% NGS). NGS reports also demonstrated discrepancies in variant classification (total 20.4%) and interpretation (total 10.2%). The rate of discrepancies generally improved year-on-year. Inter-laboratory concordance for molecular haematology testing is high in the analytical phase, however opportunities exist for improvement in the post-analytical phase. Given that result interpretation is crucial for clinical decision-making and that molecular testing is a complex and evolving field, we suggest that EQAPs should comprehensively evaluate both analytical and post-analytical components of laboratory performance in order to harmonise reporting and to support the accurate interpretation of molecular haematology tests.

UNASSIGNED: The results are presented of the inter-laboratory validation of a liquid chromatography-tandem mass spectrometry method for the determination of eight mycotoxins (aflatoxin B1, deoxynivalenol, fumonisin B1, fumonisin B2, ochratoxin A, toxin T-2, toxin HT-2 and zearalenone) in animal feeds.
UNASSIGNED: This study was an essential part of the method\'s transfer from the National Reference Laboratory to six regional laboratories in Poland working in the official survey of mycotoxins in feed. The laboratories received a batch of standard solutions, blank samples and quality control materials on which to perform analysis with one procedure and different liquid chromatography-tandem mass spectrometry conditions.
UNASSIGNED: The validation results show good precision (reproducibility coefficient of variation 3.7-20.5%) and accuracy of the method (recovery 89-120% and trueness 94-103%) and sufficient skills of the laboratory personnel.
UNASSIGNED: The study is an example of the successful transfer of the method among laboratories.

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.

BACKGROUND: Flibanserin (FLB) was first 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.
OBJECTIVE: 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.
METHODS: The HPLC separation was achieved in a Supelco Ascentis® Express series phenyl hexyl column (100 × 4.6 mm, ID 2.7 µm). 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 a LCMS-IT-TOF instrument (Shimadzu, Japan).
RESULTS: 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 the 2.5-50.0 µg/mL range. The LOD and LOQ were 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.
CONCLUSIONS: A novel FLB degradation product, which was produced under oxidative forced degradation conditions 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 a pseudo Addyi® (Sprout Pharmaceuticals, Inc.) sample was tested using both instrument configurations.
CONCLUSIONS: A novel stability-indicating assay method was developed and fully validated according to the International Council on Harmonization (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 a pseudo formulation of Addy in both instruments, and ANOVA was applied for evaluation.

The establishment of reliable and robust in vitro models for hazard assessment, a prerequisite for moving away from animal testing, requires the evaluation of model transferability and reproducibility. Lung models that can be exposed via the air, by means of an air-liquid interface (ALI) are promising in vitro models for evaluating the safety of nanomaterials (NMs) after inhalation exposure. We performed an inter-laboratory comparison study to evaluate the transferability and reproducibility of a lung model consisting of the human bronchial cell line Calu-3 as a monoculture and, to increase the physiologic relevance of the model, also as a co-culture with macrophages (either derived from the THP-1 monocyte cell line or from human blood monocytes). The lung model was exposed to NMs using the VITROCELL® Cloud12 system at physiologically relevant dose levels.
Overall, the results of the 7 participating laboratories are quite similar. After exposing Calu-3 alone and Calu-3 co-cultures with macrophages, no effects of lipopolysaccharide (LPS), quartz (DQ12) or titanium dioxide (TiO2) NM-105 particles on the cell viability and barrier integrity were detected. LPS exposure induced moderate cytokine release in the Calu-3 monoculture, albeit not statistically significant in most labs. In the co-culture models, most laboratories showed that LPS can significantly induce cytokine release (IL-6, IL-8 and TNF-α). The exposure to quartz and TiO2 particles did not induce a statistically significant increase in cytokine release in both cell models probably due to our relatively low deposited doses, which were inspired by in vivo dose levels. The intra- and inter-laboratory comparison study indicated acceptable interlaboratory variation for cell viability/toxicity (WST-1, LDH) and transepithelial electrical resistance, and relatively high inter-laboratory variation for cytokine production.
The transferability and reproducibility of a lung co-culture model and its exposure to aerosolized particles at the ALI were evaluated and recommendations were provided for performing inter-laboratory comparison studies. Although the results are promising, optimizations of the lung model (including more sensitive read-outs) and/or selection of higher deposited doses are needed to enhance its predictive value before it may be taken further towards a possible OECD guideline.

Objective: To understand the comparability of noise measurement results of various occupational hygiene technical service organizations in Guangdong Province by conducting inter-laboratory comparison of measuring instruments and personnel operation. Methods: In October 2020, the instrument comparison and personnel comparison among 91 occupational hygiene technical service organizations engaged in noise measurement in Guangdong Province were carried out in the form of fixed-point measurement and simulated workplace measurement, and the results were analyzed and evaluated by using the robust z-ratio score. Results: In the instrument comparison, 6 organizations had 1 or 2 outliers in their z-ratio scores, 2 organizations had 2 problematic values in their z-ratio scores, and a total of 8 organizations (accounting for 8.8%) were judged as unqualified; A total of 83 organizations (accounting for 91.2%) with satisfactory z-ratio scores or only one problematic value were judged as qualified. In the personnel comparison, there were 11 organizations with 1 or 2 outliers in the z-ratio score, and 1 organization with 2 problematic values in the z-ratio score. A total of 12 organizations (13.2%) were judged as unqualified and 79 organizations (accounting for 86.8%) with satisfactory z-ratio scores or only one problematic value were judged as qualified. Through comprehensive judgment, 20 organizations (22.0%) were judged as unqualified, and 71 organizations (78.0%) were judged as qualified. There was no statistically significant difference in the qualified rates of instrument comparison results, personnel comparison results and comprehensive evaluation results of non-private organizations and private organizations (P>0.05). There was no significant difference in the qualified rates of instrument comparison results and comprehensive evaluation results of qualified organizations and unqualified organizations (P>0.05), there was significant difference in the qualified rate of personnel comparison results (P<0.05) . Conclusion: The noise measurement results of some occupational health technical service organizations in Guangdong Province are generally comparable. To carry out inter-laboratory comparison of noise instrument performance and personnel operation ability of occupational hygiene technical service organizations, can comprehensively evaluate the testing process of each organization and find out the problems existing in each organization.
目的： 通过开展测量仪器及人员操作的实验室间比对，了解广东省各机构噪声测量结果的可比性。 方法： 于2020年10月，以定点测量及模拟工作场所测量两种形式开展广东省从事噪声检测及监测的91家机构实验室间仪器比对及人员比对，采用稳健z比分数对结果进行分析评估。 结果： 仪器比对中，有6家机构z比分数出现1个或2个离群值，2家机构z比分数出现2个有问题值，共8家（占8.8%）判定为不合格；83家（占91.2%）机构z比分数满意或只出现1个有问题值，判定为合格。人员比对中，有11家机构z比分数出现1个或2个离群值，1家机构z比分数出现2个有问题值，共12家（占13.2%）判定为不合格；79家（占86.8%）机构z比分数满意或只出现1个有问题值，判定为合格。综合判定，共20家（占22.0%）判定为不合格，71家（占78.0%）判定为合格。非民营机构与民营机构仪器比对结果、人员比对结果及综合评定结果合格率差异均无统计学意义（P>0.05）。有资质机构和无资质机构人员比对结果合格率差异有统计学意义（P<0.05），仪器比对结果及综合评定结果合格率差异均无统计学意义（P>0.05）。 结论： 广东省部分机构噪声测量结果可比性一般，开展机构噪声仪器性能及人员操作能力的实验室间比对，可对各机构检测过程进行全面评估，发现各机构存在的问题。.

Air-liquid interface (ALI) lung cell models cultured on permeable transwell inserts are increasingly used for respiratory hazard assessment requiring controlled aerosolization and deposition of any material on ALI cells. The approach presented herein aimed to assess the transwell insert-delivered dose of aerosolized materials using the VITROCELL® Cloud12 system, a commercially available aerosol-cell exposure system. An inter-laboratory comparison study was conducted with seven European partners having different levels of experience with the VITROCELL® Cloud12. A standard operating procedure (SOP) was developed and applied by all partners for aerosolized delivery of materials, i.e., a water-soluble molecular substance (fluorescence-spiked salt) and two poorly soluble particles, crystalline silica quartz (DQ12) and titanium dioxide nanoparticles (TiO2 NM-105). The material dose delivered to transwell inserts was quantified with spectrofluorometry (fluorescein) and with the quartz crystal microbalance (QCM) integrated in the VITROCELL® Cloud12 system. The shape and agglomeration state of the deposited particles were confirmed with transmission electron microscopy (TEM). Inter-laboratory comparison of the device-specific performance was conducted in two steps, first for molecular substances (fluorescein-spiked salt), and then for particles. Device- and/or handling-specific differences in aerosol deposition of VITROCELL® Cloud12 systems were characterized in terms of the so-called deposition factor (DF), which allows for prediction of the transwell insert-deposited particle dose from the particle concentration in the aerosolized suspension. Albeit DF varied between the different labs from 0.39 to 0.87 (mean (coefficient of variation (CV)): 0.64 (28%)), the QCM of each VITROCELL® Cloud 12 system accurately measured the respective transwell insert-deposited dose. Aerosolized delivery of DQ12 and TiO2 NM-105 particles showed good linearity (R2 > 0.95) between particle concentration of the aerosolized suspension and QCM-determined insert-delivered particle dose. The VITROCELL® Cloud 12 performance for DQ12 particles was identical to that for fluorescein-spiked salt, i.e., the ratio of measured and salt-predicted dose was 1.0 (29%). On the other hand, a ca. 2-fold reduced dose was observed for TiO2 NM-105 (0.54 (41%)), which was likely due to partial retention of TiO2 NM-105 agglomerates in the vibrating mesh nebulizer of the VITROCELL® Cloud12. This inter-laboratory comparison demonstrates that the QCM integrated in the VITROCELL® Cloud 12 is a reliable tool for dosimetry, which accounts for potential variations of the transwell insert-delivered dose due to device-, handling- and/or material-specific effects. With the detailed protocol presented herein, all seven partner laboratories were able to demonstrate dose-controlled aerosolization of material suspensions using the VITROCELL® Cloud12 exposure system at dose levels relevant for observing in vitro hazard responses. This is an important step towards regulatory approved implementation of ALI lung cell cultures for in vitro hazard assessment of aerosolized materials.

Nanoparticles including nanomedicines are known to be recognised by and interact with the immune system. As these interactions may result in adverse effects, for safety evaluation, the presence of such interactions needs to be investigated. Nanomedicines in particular should not unintendedly interact with the immune system, since patient\'s exposure is not minimised as in the case of \'environmental\' nanoparticles, and repeated exposure may be required. NLRP3 inflammasome activation and dendritic cell (DC) maturation are two types of immune mechanisms known to be affected by nanoparticles including nanomedicines. NLRP3 inflammasome activation results in production of the pro-inflammatory cytokines IL-1β and IL-18, as well as a specific type of cell death, pyroptosis. Moreover, chronic NLRP3 inflammasome activation has been related to several chronic diseases. Upon maturation, DC activate primary T cells; interference with this process may result in inappropriate activation and skewing of the adaptive immune response. Here, we evaluated the effect of two nanomedicines, representing nanostructured lipid carriers and polymers, on these two assays. Moreover, with a view to possible future standardisation and regulatory application, these assays were subject to an inter-laboratory comparison study using common SOPs. One laboratory performed three independent NLRP3 inflammasome activation experiments, while the other performed a single experiment. Two laboratories each performed three independent DC maturation experiments. While the nanostructured lipid carrier only showed marginal effects, the polymers showed major cytotoxicity. No evidence for inflammasome activation or DC maturation was demonstrated. Intra- and inter-laboratory comparison showed clearly reproducible results.

Over the past few decades, the metal elements (MEs) in atmospheric particles have aroused great attention. Some well-established techniques have been used to measure particle-bound MEs. However, each method has its own advantages and disadvantages in terms of complexity, accuracy, and specific elements of interest. In this study, the performances of inductively coupled plasma-optical emission spectrometry (ICP-OES) and total reflection X-ray fluorescence spectroscopy (TXRF) were evaluated for quality control to analyze data accuracy and precision. The statistic methods (Deming regression and significance testing) were applied for intercomparison between ICP-OES and TXRF measurements for same low-loading PM2.5 samples in Weizhou Island. The results from the replicate analysis of standard filters (SRM 2783) and field filters samples indicated that 10 MEs (K, Ca, V, Cr, Mn, Fe, Ni, Cu, Zn, and Pb) showed good accuracies and precision for both techniques. The higher accuracy tended to the higher precision in the MEs analysis process. In addition, the interlab comparisons illustrated that V and Mn all had good agreements between ICP-OES and TXRF. The measurements of K, Cu and Zn were more reliable by TXRF analysis for low-loading PM2.5. ICP-OES was more accurate for the determinations for Ca, Cr, Ni and Pb, owing to the overlapping spectral lines and low sensitivity during TXRF analysis. The measurements of Fe, influenced by low-loading PM2.5, were not able to determine which instrument could obtain more reliable results. These conclusions could provide reference information to choose suitable instrument for the determination of MEs in low-loading PM2.5 samples.