Expanded Measurement Uncertainty Research Articles

Determination of the Nanoscale Silica Mass Fraction by AF4/ICP-MS with Isotope Dilution Analysis Using 29Si-Enriched Silica Nanoparticles.

A methodology based on the use of asymmetrical flow field-flow fractionation (AF4) coupled to ICP-MS with size fraction-targeted isotope dilution analysis (IDA) has been developed, validated, and applied for the first time to determine the mass fraction of nanoscale silica (SiO2). For this purpose, 29Si-enriched SiO2 nanoparticles, to be used as an IDA spike/internal standard, were synthesized and characterized in-house. Double IDA was used to quantify an aqueous suspension of Stöber silica particles of similar characteristics to those of the 29SiO2 nanoparticle (NP) spike using a representative test material of natural Si isotopic composition as the calibrant. For fumed SiO2 NP in a highly complex food matrix, a methodology based on single IDA with AF4/ICP-MS using the same 29SiO2 NP spike was developed and validated. Relative expanded measurement uncertainties (k = 2) of 4% (double IDA) and 8% (single IDA) were achieved for nanoscale silica mass fractions of 5143 and 107 mg kg-1 in water suspension and food matrix, respectively. To assess the accuracy of AF4/ICP-IDMS for the characterization of SiO2 NP in a food matrix, standard addition measurements on samples spiked with Aerosil AF200, also in-house characterized for Si mass fraction, were undertaken, with an average recovery of 95.6 ± 4.1% (RSD, n = 3) obtained. The particle-specific IDA data obtained for both SiO2 NP-containing samples were also compared with that of post-AF4 channel external calibration using inorganic Si standards. The mass fractions obtained by IDA agreed well with those obtained by external calibration within their associated measurement uncertainties.

Improved coverage factors for expanded measurement uncertainty calculated from two estimated variance components

Measurement uncertainty (MU) arising at different stages of a measurement process can be estimated using analysis of variance (ANOVA) on replicated measurements. It is common practice to derive an expanded MU by multiplying the resulting standard deviation by a coverage factor k. This coverage factor then defines an interval around a measurement value within which the value of the measurand, or true value, is asserted to lie for a desired confidence level (e.g. 95 %). A value of k = 2 is often used to obtain approximate 95 % coverage, although k = 2 will be an underestimate when the standard deviation is estimated from a limited amount of data. An alternative is to use Student’s t-distribution to provide a value for k, but this requires an exact or approximate degrees of freedom (df). This paper explores two different methods of deriving an appropriate k in the case when two variances from an ANOVA (classical or robust) need to be combined to estimate the measurement variance. Simulations show that both methods using the modified coverage factor generally produce a confidence interval much closer to the desired level (e.g. 95 %) when the data are approximately normally distributed. When these confidence intervals do deviate from 95 %, they are consistently conservative (i.e. reported coverage is higher than the nominal 95 %). When outlying values are included at the level of the larger variance component, in some cases the method used for robust ANOVA produces confidence intervals that are very conservative.

Advanced methods for the detection of measurement outliers in fibre optic strain measurements for non-destructive monitoring of the structural health of composite over-wrapped pressure vessels of type-IV

To analyse the applicability of fibre optic measurements as a measurement method for structural health monitoring, fibre-optic sensors are placed on the vessel surface. The influence of the surface profile of the vessel on the measurement result is analysed by correlating the 3D scanned surface and measurement results. One outcome is that the measurement is substantially influenced by the surface topography. The surface height can be directly correlated to the strain magnitude, which is also verified by analytical calculations. Outliers and invalid values can be traced back to surface-related influences on the sensor fibre. For the outlier detection, a novel method is presented, which is based on quantitative evaluation criteria and inductive reasoning and enables transient cycle- by-cycle outlier detection adapted to the load case. Based on the results an estimate for the expanded measurement uncertainty is given for of the measurement chain consisting of vessel, adhesive and sensor fibre.

Determination of intrinsic energy dependence of point-like inorganic scintillation detector in brachytherapy.

Inorganic scintillation detectors (ISDs) are promising for in vivo dosimetry in brachytherapy (BT). ISDs have fast response, providing time resolved dose rate information, and high sensitivity, attributed to high atomic numbers. However, the conversion of the detector signal to absorbed dose-to-water is highly dependent on the energy spectrum of the incident radiation. This dependence is comprised of absorbed dose energy dependence, obtainable with Monte Carlo (MC) simulation, and the absorbed dose-to-signal conversion efficiency or intrinsic energy dependence requiring measurements. Studies have indicated negligible intrinsic energy dependence of ZnSe:O-based ISDs in Ir-192 BT. A full characterization has not been performed earlier. This study characterizes the intrinsic energy dependence of ZnSe:O-based ISDs for kV X-ray radiation qualities, with energies relevant for BT. Three point-like ISDs made from fiber-coupled cuboid ZnSe:O-based scintillators were calibrated at the Swedish National Metrology Laboratory for ionizing radiation. The calibration was done in terms of air kerma free-in-air, Kair , in 13 X-ray radiation qualities, Q, from 25 to 300 kVp (CCRI 25-250kV and ISO 4037 N-series), and in terms of absorbed dose to water, Dw , in a Co-60 beam, Q0 . The mean absorbed dose to the ISDs, relative to Kair and Dw , were obtained with the MC code TOPAS (Geant4) using X-ray spectra obtained with SpekPy software and laboratory filtration data and a generic Co-60 source. The intrinsic energy dependence was determined as a function of effective photon energy, , (relative to Co-60). The angular dependence of the ISD signal was measured in a 25 kVp (0.20mm Al HVL) and 135 kVp beam (0.48mm Cu HVL), by rotating the ISDs 180° around the fiber's longitudinal axis (perpendicular to the beam). A full 360° was not performed due to setup limitations. The impact of detector design was quantified with MC simulation. Above 30keV the intrinsic energy dependence varied with less than 5±4% from unity for all detectors (with the uncertainty expressed as the mean of all expanded measurement uncertainties for individual above 30keV, k=2). Below 30keV, it decreased with up to 17% and inter-detector variations of 13% were observed, likely due to differences in detector geometry not captured by the simulations using nominal geometry. In the 25 kVp radiation quality, the ISD signal varied with 24% over a ∼45° rotation. For 135 kVp, the corresponding variation was below 3%. Assuming a 0.05mm thicker layer of reflective paint around the sensitive volume changed the absorbed dose with 6.3% at the lowest , and with less than 2% at higher energies. The study suggests that the ISDs have an intrinsic energy dependence relative to Co-60 lower than 5±4% in radiation qualities with >30keV. Therefore, they could in principle be calibrated in a Co-60 beam quality and transferred to such radiation qualities with correction factors determined only by the absorbed dose energy dependence obtained from MC simulations. This encourages exploration of the ISDs' applications in intensity modulated BT with Yb-169 or other novel intermediate energy isotopes.

Validation of a Targeted LC-MS/MS Method for Cereulide and Application in Food and Faeces.

Cereulide is an emetic toxin produced by some strains of Bacillus cereus. This bacterial toxin, a cyclic 1.2 kDa dodecadepsipeptide, is stable to heat and acids and causes nausea and vomiting when ingested via contaminated food. This work aimed to develop and validate a targeted analytical method applying liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify this toxin in food and human faeces. Samples were extracted with acetonitrile in the presence of 13C6-cereulide, a labelled internal standard, and purified by centrifugation and filtration. The limits of quantification were 0.5 and 0.3 µg kg-1 for food and faeces, respectively. The linearity of the method was very good, with calculated R2 values above 0.995. The mean recovery of the method was within the acceptable range of 70.0%-120.0%, the repeatability was not higher than 7.3%, and the highest intra-laboratory reproducibility was 8.9%. The estimated range for the expanded measurement uncertainty was between 5.1% and 18.0%. The LC-MS/MS method was used to analyse one food sample (rice) from a Belgian foodborne outbreak and five faecal samples from patients with clinical symptoms after consumption of the contaminated rice. The levels of cereulide were 12.22 µg g-1 for food and between 6.32 and 773.37 ng g-1 for faecal samples.

Sub-micron inline thickness measurement of cold-rolled metal strips by multi-wavelength interferometry and laser triangulation.

Thin metal foils of thicknesses below 100 µm are finding increasing use in high-tech applications. For such foils it is essential that production be controlled inline with sub-micron accuracy in highly challenging environments. An optical thickness gauge combining laser triangulation with multi-wavelength interferometry has now been developed for this purpose. Modulation-based 2f-3f-interferometry was used to realize a compact and robust sensor. A thorough measurement uncertainty analysis of the complete thickness measurement process yielded an expanded measurement uncertainty of U=(0.30μm)2+4π R a2, which is dependent on the roughness average Ra. The influence of oil remnants on measurement results is significantly weaker in the interference measurement than in geometric optical systems. Verification measurements against tactile reference measurements support the derived measurement uncertainty, and initial measurements in actual rolling mill environments have proven the real-world capability of this measurement technique over relevant process time scales at metal strip speeds of 200 m/min.

Simultaneous determination of macrolides in water samples by solid-phase extraction and capillary electrophoresis.

Solid-phase extraction (SPE) coupled with capillary electrophoresis (CE) for the determination of macrolide antibiotics (azithromycin, clarithromycin, roxithromycin, tylosin) and tiamulin in water samples was described in this article. These compounds were extracted with different types of sorbents ( Oasis HLB, C18, C8, SDB, and Strata-X) and different masses of sorbents (60 mg, 200 mg, and 500 mg) using different organic solvents (methanol, ethanol, and acetonitrile) and different pH values of water samples (pH 7.00, 8.00, and 9.00). It was found that the highest extraction efficiency of the studied compounds was obtained with 200 mg/3 mL C18 cartridges with methanol as eluent at pH 9.00 of the water sample. The developed SPE-CE method for macrolide antibiotics and tiamulin was validated for linearity, precision, repeatability, the limit of detection (LOD), the limit of quantification (LOQ), and recovery. Good linearity was obtained in the range of 0.3-30 mg L-1 depending on the drug, with correlation coefficients higher than 0.9958 in all cases except clarithromycin (0.9873). Expanded measurement uncertainties were calculated for each pharmaceutical, accounting for 20.31 % (azithromycin), 38.33 % (tiamulin), 28.95 % (clarithromycin), 26.99 % (roxithromycin), and 21.09 % (tiamulin). Uncertainties associated with precision and calibration curves contributed the most to the combined measurement uncertainty. The method was successfully applied to the analysis of production waste-water from the pharmaceutical industry.

Inf uence of the variable geometry of the diverter nozzle on the metrological characteristics of a calibration unit with weighing devices

This article discusses the issues of improving the metrological characteristics, weight-dimensional and technical and economic indicators of calibration installations with weighing devices due to the introduction of a fl ow switch with a variable nozzle exit geometry into their design. It is assumed that the use of this design of the fl ow switch will solve the problem of fi lling the nozzle exit with water, reduce the dimensions of the hydraulic path, simplify the maintenance procedure, and reduce the cost of installations. A description of the design, principles of operation and a timing diagram of a fl ow switch with a variable nozzle exit geometry are presented. The local hydrodynamic characteristics of the water fl ow by a Pitot tube in the nozzle exit are studied with a change in its width in the mass fl ow rate range from 25 to 550 t/h. The optimal values of the nozzle cut width are experimentally determined depending on the value of the mass fl ow rate of the liquid, at which it is completely fi lled with liquid. A study of the metrological characteristics of a calibration installation with weighing devices, which includes a fl ow switch with a variable nozzle exit geometry, methods of indirect measurements and comparisons using a comparison standard in a wide range of liquid mass fl ow rates, has been carried out. The impact on the metrological characteristics of a calibration installation with weighing devices of the nozzle cut width in the investigated range of liquid fl ow is established. Graphical dependences of the expanded measurement uncertainty of the installation when reproducing the unit of liquid mass fl ow rate on the measurement time interval and on the mass fl ow rate of the liquid are presented. Based on the research results, the optimal values of the nozzle cut width and measurement time intervals were determined depending on the mass fl ow rates of the liquid when using a fl ow switch with a variable nozzle cut geometry. The expansion of the range of operation of weighing devices, which are part of the verifi cation installations with weighing devices, is justifi ed. According to the results of the research, the proposed design of the fl ow switch with a variable geometry of the nozzle exit is recommended for use in the design of new and modernization of installations for calibration with weight devices of fl ow switches.

An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure for the quantification of topiramate in human serum and plasma.

Topiramate is an antiepileptic drug (AED) used for the monotherapy or adjunctive treatment of epilepsy and for the prophylaxis of migraine. It has several pharmacodynamic properties that contribute to both its clinically useful properties and observed adverse effects. Accurate measurement of its concentration is therefore essential for dose adjustment/optimisation of AED therapy. Our aim was to develop and validate a novel reference measurement procedure (RMP) for the quantification of topiramate in human serum and plasma. An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method in combination with a protein-precipitation-based sample preparation allows for quantification of topiramate in human serum and plasma. To assure traceability to SI units, quantitative nuclear magnetic resonance (qNMR) was applied to characterize the reference material used as primary calibrator for this RMP. Matrix effects were determined by performing a post-column infusion experiment and comparing standard line slopes. Accuracy and precision was evaluated performing an extensive five day precision experiment and measurement uncertainty was evaluated according Guide to the Expression of Uncertainty in Measurement (GUM). The method enabled topiramate quantification within the range of 1.20-36.0 μg/mL without interference from structurally related compounds and no evidence of a matrix effect. Intermediate precision was≤3.2 % and repeatability was 1.4-2.5 % across all concentration levels. The relative mean bias was-0.3 to 3.5 %. Expanded measurement uncertainties for target value assignment (n=6) were found to be≤2.9 % (k=2) independent of the concentration level and the nature of the sample. In human serum and plasma, the RMP demonstrated high analytical performance for topiramate quantification and fulfilled the requirements on measurement uncertainty. Traceability to SI units was established by qNMR content determination of the topiramate, which was used for direct calibration of the RMP. This RMP is, therefore, fit for purpose for routine assay standardization and clinical sample evaluation.

A high precision VIS/NIR dynamic goniometer-spectrometer

We present a method for measuring the refractive index (RI) and spectral characteristics of transparent triangular prisms based on the minimum deviation technique. The proposed method has been developed to automatically measure RI simultaneously for three different wavelengths to determine the spectral dependence of RI. A high precision dynamic goniometer with a He-Ne ring laser and continuously rotating autocollimation mirror was used to implement the proposed method. A set of reference prisms made of optical glass were experimentally studied and the measurement uncertainty budget was estimated. The obtained values of the expanded measurement uncertainty did not exceed 4.6 × 10−6 for near-infrared and 1.2 × 10−5 for visible wavelength ranges with a coverage factor k = 2 (95% level of confidence). It is shown that this method can be used for high-precision measurements of the RI and determine the spectral characteristics.

Presence of 6PPD-quinone in runoff water samples from Norway using a new LC–MS/MS method

The chemical 6PPD-quinone is highly toxic to some fish species of the Oncorhynchus and Salvelinus genera and is the oxidation product of the common car tire additive 6PPD. We present a new sample preparation method that involves liquid-liquid extraction of water samples followed by silica-based solid phase extraction prior to LC–MS/MS analysis. The new sample preparation method showed good analyte recovery from spiked water samples (78%–91%) and a low ion suppression effect, surpassing previously published methods. This new method was successfully validated, achieving a limit of quantification of 5 ng/L and estimated expanded measurement uncertainty of 18.6%. In a proof-of-concept study, the method was applied to several water samples from various sources in Southern Norway. These were runoff samples from tunnel washing, from a tunnel runoff treatment plant and downstream of the plant drain. In addition, two water samples from puddles were included: one was run-off from an artificial soccer turf field and one from a puddle on a country road. The results of the analyses revealed that the concentration of 6PPD-quinone was above the LC50 reported for coho salmon (Oncorhynchus kisutch) in all samples except the samples from and downstream of the treatment plant. The highest measured concentration was 258 ng/L, which is the 2.7-fold of the reported LC50 in coho salmon (95 ng/L). Our initial data emphasize the need for more comprehensive environmental monitoring of 6PPD-quinone as well as toxicological studies in aquatic organisms.

Measurement of critical properties for the binary mixture of R744 (carbon dioxide) + R1234ze(E) (trans-1,3,3,3-tetrafluoropropene)

In the context of global warming and demanding alternative refrigerants, the transcritical CO2 refrigeration cycle was considered a potentially energy-saving and carbon-reducing technology. The use of CO2 mixtures with higher critical temperatures and lower critical pressures has been demonstrated as an effective way to improve the performance of transcritical CO2 refrigeration cycles. To achieve this approach, accurate critical locus parameters are needed for establishing cross-over state equations and calculating thermodynamic properties in the near-critical region. Currently, experimental methods are the most effective way to obtain high-precision critical locus parameters of mixtures. In this work, the critical properties including critical temperature, critical pressure, critical density, and mole fraction of the R744 (carbon dioxide) + R1234ze(E) (trans-1,3,3,3-tetrafluoropropene) binary mixture were measured according to a variable-volume method with a metal-bellows volumeter. The critical point was determined by visual observation of the critical opalescence and reappearance of the vapor-liquid meniscus. The combined expanded measurement (relative) uncertainties of the critical temperature, critical pressure, critical density, and mole fraction were within 50 mK, 0.021 MPa, 0.6%, and 0.012 (k = 2, 0.95 level of confidence), respectively. After comparing the fitting results of the Modified Chueh-Prausnitz (MCP) method, the Modified Wilson (MW) method, and the Redlich-Kister (RK) method. We recommended the Modified Wilson method to correlate the critical properties of the binary system of R1234ze(E)+R744. Our research showed that R1234ze(E)+R744 mixture can achieve a higher critical temperature and critical density simultaneously and a lower critical pressure compared with pure CO2 when the composition of R744 is less than 0.23.

Accounting for the distributions of input quantities in the procedure for the measurement uncertainty evaluation when calibrating the goniometer

The discords concerning the measurement uncertainty evaluation in the Guide to the Expressing of Uncertainty in Measurement (GUM) and its Supplement 1 are considered. To overcome these discords, the authors of the paper propose to use the kurtosis method and the law of the propagation of the expanded uncertainty. Using the example of the goniometer calibration, the features of accounting for the distribution laws of input quantities in the procedure for the measurement uncertainty evaluation are shown. A model for direct measurements of the value of a reference measure of the angle using a goniometer is written, the procedures for the measurement uncertainty evaluation are described, and uncertainty budgets for each of the methods are given. An example of the measurement uncertainty evaluation when calibrating a digital goniometer using a 24-sided reference prism is described. An estimate of the expanded measurement uncertainty for this example was made based on the web-based software application NIST Uncertainty Machine, which showed a good agreement with the estimates obtained by the considered methods. The technology of applying this software application for the confidence level of 0,9545, which the software lacks, is shown. The estimates of the measurement uncertainty obtained by the proposed methods, Monte Carlo method and methodology of the Guide to the Expressing of Uncertainty in Measurement are compared.

An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure for the quantification of levetiracetam in human serum and plasma.

To develop an isotope dilution-liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based candidate reference measurement procedure (RMP) for levetiracetam quantification in human serum and plasma. Quantitative nuclear magnetic resonance spectroscopy (qNMR) was used to characterize the RMP material to ensure traceability to SI units. To quantify levetiracetam, an LC-MS/MS method was optimized using a C8 column for chromatographic separation following protein-precipitation-based sample preparation. Spiked matrix samples of serum and plasma were used to test selectivity and specificity. Matrix effects were determined by performing a post-column infusion experiment and comparing standard line slopes. Precision and accuracy were evaluated over 5days. Measurement uncertainty was evaluated according to the Guide to the Expression of Uncertainty in Measurement (GUM). The RMP was proven to be highly selective and specific with no evidence of a matrix effect, allowing for quantification of levetiracetam within the range of 1.53-90.0μg/mL. Intermediate precision was <2.2% and repeatability was 1.1-1.7% across all concentrations. The relative mean bias ranged from-2.5% to-0.3% across all levels and matrices within the measuring range. Diluted samples were found with a mean bias ranging from-0.1 to 2.9%. The predefined acceptance criterion for measurement uncertainty was met and determined for individual measurements independently of the concentration level and sample type to be≤4.0% (k=2). We present a novel LC-MS/MS)-based candidate RMP for levetiracetam in human serum and plasma. Its expanded measurement uncertainty of≤4.0% meets the clinical needs in levetiracetam monitoring. Utilizing qNMR to characterize levetiracetam reference materials allowed metrological traceability to SI units.

Design and Experimental Study of a Probe for Crankshaft Full-automatic Measuring Machine

Abstract The Crankshaft Full-automatic Measuring Machine (CFMM) features high accuracy, high efficiency and complete measurement parameters, and represents the forefront of a geometric crankshaft accuracy measuring instrument. One of its core technologies is the high-precision radial following the crankshaft connecting rod journal measurement. In this paper, an independent probe design scheme combining the flexible dual-complex parallel four-bar guide mechanism and double displacement sensors based on the contact measurement method was proposed. It was suitable for the measurement of precision parts with eccentric characteristics such as crankshaft and camshaft measurement. Taking the spring as the flexible part, the probe prototype’s optimization design, processing and assembly were completed, the test device was built, and the system accuracy was calibrated under various positions and feed quantities of the probe. The results revealed that the expanded measurement uncertainty after double-sensor compensation was enhanced from 1.53 μm in single-sensor measurement to 0.44 μm, satisfying the high-precision requirements of engineering measurement accuracy and reducing the measurement cost.

Using the gamma spectrometry method to determine the concentration of radon in samples of mineral radon water

The results of a study on the choice of the optimal measurement geometry, measuring capacity and method of sealing the measuring capacity for determining the concentration of radon-222 in samples of mineral radon water are presented. Studies of radon water samples were carried out in laboratory conditions on a stationary gamma spectrometer based on a semiconductor Ge(Li) detector. The concentration measurements in the samples were carried out in accordance with MVI. MN 3421-2010 “Methodology for measuring the volumetric and concentration of gamma-emitting radionuclides on gamma spectrometers with semiconductor detectors” for standard plastic vessels “Denta, 0.1 l” and “Marinelli, 1 l”, and glass containers with a volume of 0.5 l with lids for twisting and seaming. The results of the research showed that the leakage of radon from a glass container with a metal lid for sealing is minimal. This method of sampling and sealing the measuring vessel makes it possible to increase the accuracy of the presented measurement results by reducing the corrections for sample preparation when calculating the expanded measurement uncertainty. A glass container with a volume of 0.5 l with a metal cap for seaming was used to measure the concentration of radon in samples of mineral radon water taken from wells and a drinking fountain of the Radon sanatorium of Belagrozdravnitsa JSC (Dyatlovo District, Grodno Region). The concentration range was 760–2100 Bq/kg. The selected measuring container, the method of its sealing and the measurement geometry can be used for future measurements of the radon concentration in samples of mineral radon water taken in the sanatoriums of the Republic of Belarus.

Development of measures for metrological support of Raman spectroscopy

The method of Raman spectroscopy (RS) is widely used for timely metrological support of technological lines of the industrial sector in the chemical, medical and pharmaceutical, food, as well as criminalistics and forensic examinations. The wide application of the Raman spectroscopy method requires the use of specific metrological support tools, namely, measures for calibrating Raman spectrometers and microscopes according to the spectrum shape (i. e. relative spectral sensitivity).The purpose of the research was to develop prototype measures designed to calibrate Raman spectrometers and microscopes on a scale of relative intensities provided with metrological traceability to the SI base units.Prototype measures were made from inorganic glasses based on an oxide matrix, each of the glasses was activated with metal ions selected to excite a broad fluorescence line with radiation at a given wavelength: 532 nm (manganese ions), 633 nm (bismuth ions) and 785 nm (chromium ions). Metrological characteristics were established for prototype measures, where the certified characteristic is the relative intensity of the reproduced fluorescence radiation. The maximum expanded measurement uncertainty of the relative fluorescence intensity at a coverage factor k = 2 was determined, which is 9.4 %, 5.2 % and 2.8 % for prototype measures designed to reproduce the relative fluorescence intensity when excited at wavelengths of 532 nm, 633 nm and 785 nm, respectively.Certification of measures performed on the laser Raman confocal microscope Confotec NR500, which is part of the GET 196-2015 standard, allows establishing metrological traceability through the scale of relative intensities of the GET 8 6-2017 microscope, providing traceability to SI units of the “(light) energy flux” value. Thus, it is possible to find the spectral correction function for determining the Raman spectra traceable to the State Primary Standard GET 196-2015 for calibrated devices using certified measures.The practical significance of the results of the research makes it possible to expand the possibility of establishing and monitoring the stability of the calibration characteristics of microscopes and Raman spectrometers, namely, it allows calibration on a scale of relative intensities.

Traceable efficiency determination of a 2.75 MW nacelle on a test bench

In this paper, the efficiency of a 2.75 MW nacelle drivetrain on a test bench was determined traceably at various load points. For this purpose, so-called transfer standards for mechanical and electrical power measurement were additionally installed and integrated into the nacelle drivetrain. As torque measurement contributes greatly to the overall uncertainty, the static torque calibration was expanded to include additional influences present under rotation. An overall system efficiency of 89% was measured in the high torque and high speed range. The relative expanded measurement uncertainty for efficiency determination was between 0.30% and 0.72% over the entire operating range. Both the efficiency and the relative expanded measurement uncertainty were calculated for each operating point.

An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of methotrexate in human serum and plasma.

To develop an isotope dilution-liquid chromatography-tandem mass spectrometry-(ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for quantification of methotrexate in human serum and plasma. Quantitative nuclear magnetic resonance (qNMR) was used to determine absolute methotrexate content in the standard. Separation was achieved on a biphenyl reversed-phase analytical column with mobile phases based on water and acetonitrile, both containing 0.1% formic acid. Sample preparation included protein precipitation in combination with high sample dilution, and method validation according to current guidelines. The following were assessed: selectivity (using analyte-spiked samples, and relevant structural-related compounds and interferences); specificity and matrix effects (via post-column infusion and comparison of human matrix vs. neat samples); precision and accuracy (in a five-day validation analysis). RMP results were compared between two independent laboratories. Measurement uncertainty was evaluated according to current guidelines. The RMP separated methotrexate from potentially interfering compounds and enabled measurement over a calibration range of 7.200-5,700ng/mL (0.01584-12.54μmol/L), with no evidence of matrix effects. All pre-defined acceptance criteria were met; intermediate precision was≤4.3% and repeatability 1.5-2.1% for all analyte concentrations. Bias was-3.0 to 2.1% for samples within the measuring range and 0.8-4.5% for diluted samples, independent of the sample matrix. RMP results equivalence was demonstrated between two independent laboratories (Pearson correlation coefficient 0.997). Expanded measurement uncertainty of target value-assigned samples was≤3.4%. This ID-LC-MS/MS-based approach provides a candidate RMP for methotrexate quantification. Traceability of methotrexate standard and the LC-MS/MS platform were assured by qNMR assessment and extensive method validation.

An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of gabapentin in human serum and plasma.

To describe and validate a reference measurement procedure (RMP) for gabapentin, employing quantitative nuclear magnetic resonance (qNMR) spectroscopy to determine the absolute content of the standard materials in combination with isotope dilution-liquid chromatograph-tandem mass spectrometry (ID-LC-MS/MS) to accurately measure serum and plasma concentrations. A sample preparation protocol based on protein precipitation in combination with LC-MS/MS analysis using a C8 column for chromatographic separation was established for the quantification of gabapentin. Assay validation anddetermination of measurement uncertainty were performed according to guidance from the Clinical and Laboratory Standards Institute, the International Conference on Harmonization, and the Guide to the expression of uncertainty in measurement. ID-LC-MS/MS parameters evaluated included selectivity, specificity, matrix effects, precision and accuracy, inter-laboratory equivalence, and uncertainty of measurement. The use of qNMR provided traceability to International System (SI) units. The chromatographic assay was highly selective, allowing baseline separation of gabapentin and the gabapentin-lactam impurity, without observable matrix effects. Variability between injections, preparations, calibrations, and days (intermediate precision) was <2.3%, independent of the matrix, while the coefficient of variation for repeatability was 0.9-2.0% across all concentration levels. The relative mean bias ranged from-0.8-1.0% for serum and plasma samples. Passing-Bablok regression analysis indicated very good inter-laboratory agreement; the slope was 1.00 (95% confidence interval [CI] 0.98 to 1.03) and the intercept was-0.05 (95% CI -0.14 to 0.03). Pearson's correlation coefficient was≥0.996. Expanded measurement uncertainties for single measurements were found to be≤5.0% (k=2). This analytical protocol for gabapentin, utilizing traceable and selective qNMR and ID-LC-MS/MS techniques, allows for the standardization of routine tests and the reliable evaluation of clinical samples.