Joint Committee For Traceability In Laboratory Medicine Research Articles

Implementing metrological traceability of C-reactive protein measurements: consensus summary from the Joint Committee for Traceability in Laboratory Medicine Workshop.

The Joint Committee for Traceability in Laboratory Medicine (JCTLM) currently lists the secondary commutable certified reference material (CRM) ERM DA-474/IFCC (DA-474) "C-Reactive Protein in Human Serum" and two generic immunoassay-based method principles as the basis for implementing the metrological traceability of C-reactive protein (CRP) measurements by end-user measurement procedures used by medical laboratories. The current metrological traceability has produced well harmonized results for clinical samples among different end-user measurement procedures. New higher-order pure substance and secondary commutable CRMs have been nominated for listing by the JCTLM. However, the data supporting performance of these new candidate CRMs, including use of new mass spectrometry based candidate reference measurement procedures (RMPs), was not clear regarding the influence that introducing these new CRMs would have on the current well harmonized results achieved with the existing metrological traceability to DA-474. The clinically relevant CRP measurand in blood serum or plasma is a pentamer of identical subunits, which adds complexity to the application of higher-order CRMs and RMPs. The JCTLM convened a workshop in December 2022 to review the appropriate implementation of metrological traceability of CRP measurements. The workshop consensus was that the extent-of-equivalence data must include considerations about the impact of a new CRM when used for its intended purpose in the calibration hierarchies of existing end-user measuring systems; and that a new RMP must compare results with another existing well validated candidate RMP or with a globally available end-user measurement system.

Establishing metrological traceability for small molecule measurands in laboratory medicine.

For molecules that can be well described metrologically in the sense of the definition of measurands, and which can also be recorded analytically as individual substances, reference measurement service traceability to a metrologically sound foundation is a necessity. The establishment of traceability chains must be initiated by National Metrology Institutes (NMIs) according to applicable standards; they are at the top and leading position in this concept. If NMIs are not in the position to take up this task, alternative approaches must be sought. Traceability initiatives established by in vitro device industry or academia must meet the quality standards of NMIs. Adherence to International Organization for Standardization (ISO) procedure 15193 must be a matter of course for the establishment of reference measurement procedures (RMPs). Certified reference material (CRM) characterization must be thorough, e.g., by the application of quantitative nuclear magnetic resonance measurements and by adherence to ISO 15194. Both for RMPs and CRMs Joint Committee for Traceability in Laboratory Medicine (JCTLM) listing must be the ultimate goal. Results must be shared in a transparent manner to allow other stakeholders including NMIs to reproduce and disseminate the reference measurement procedures.

Quantitation of plasma metanephrines using isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS): a candidate reference measurement procedure and its application to evaluating routine ID-LC/MS/MS methods.

Accurate measurement of plasma metanephrines (MNs) including metanephrine (MN) and normetanephrine (NMN) is crucial for the screening and diagnosis in pheochromocytomas and paragangliomas (PPGLs). Although the number of laboratories using liquid chromatography tandem mass spectrometry (LC-MS/MS) method to measure MNs has been increasing rapidly, those laboratory-developed assays showed incomparable results. There are no reference measurement procedures (RMPs) or reference materials (RMs) for MNs in Joint Committee for Traceability in Laboratory Medicine (JCTLM), which hindered the standardization of MNs measurement. We established a candidate RMP (cRMP) based on isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS) method for plasma MNs measurement. Plasma samples were spiked with MN-D3 and NMN-D3 as internal standards; protein precipitation and ion-exchange solidphase extraction (SPE) were performed to extract samples, eventually analyzed by LC-MS/MS. The cRMP was applied to evaluate two routine ID-LC/MS/MS methods through split-sample comparisons. Fifty-three individual patient samples were determined by cRMP and two routine ID-LC/MS/MS methods; results were analyzed by ordinary linear regression and Bland-Altman plots. The cRMP exhibited desirable imprecision, with intra-run and total imprecision (coefficient variation, CV) for MN being 0.79-1.36% and 1.53-1.87% and for NMN being 1.10-1.34% and 1.15-1.64%. The analytical recoveries of MN and NMN ranged from 98.3 to 101.7% and from 98.5 to 101.9%, respectively. Significant calibrator biases and sample-specific deviations were observed in method comparison. An accurate, precise, and reliable cRMP for plasma MNs was developed, and RMs with value assigned following the cRMP would help minimize the calibration bias and improve the comparability of different measuring systems.

Establishment and application of an isotope dilution chromatography tandem mass spectrometry reference method for Hcy quantification

Objective To establish a reference measurement procedure for the determination of human serum homocysteine by isotope dilution high performance liquid chromatography-tandem mass spectrometry (ID-LC/MS/MS), and to apply it to establish sample target values for external quality assessment (EQA) in clinical laboratories. Methods The reference method of Hcyquantification in our laboratory was establishedaccording to the method recommended by the Joint Committee for Traceability in Laboratory Medicine (JCTLM). The precision, trueness, specificity, residue and matrix effect of the method were evaluated. The reference method was applied to establish Hcy target values for samples of the second EQA in Shanghai of 2018. Results The method detects 12.5μmol/L and 37.4μmol/L samples in three batches in three days, and the CV between batches is 1.03% and 2.10%, respectively. The measured values of Standard reference material (SRM) 1955 of National Institute of Standards and Technology (NIST) were within the specified uncertainty range. No matrix effect and carryover were observed. The second EQA data in 2018 showed that the average value of domestic reagent group was lower than that of reference method, and that of imported reagent group was higher than that of reference method. Conclusion Thereference measurement procedure of ID-LC/MS/MS was successfully established to determine the human serum homocysteine. It is expected to play a role in tracing the quantities of Hcy in clinical laboratories. Key words: Homocysteine; Chromatography, liquid; Tandem mass spectrometry; Reference values; Reference standards

Estimating uncertainty of target values for DEQAS serum materials

The External Quality Assessment (EQA) scheme for vitamin D metabolites (DEQAS) distributes human serum samples to laboratories across the world to assess their performance in measuring serum total 25-hydroxyvitamin D [25(OH)D], i.e. the sum of the concentrations of serum 25(OH)D2 and 25(OH)D3. In 2013 DEQAS, in collaboration with the Vitamin D Standardization Program (VDSP), became an accuracy-based EQAS when the National Institute for Standards and Technology (NIST) began assigning 25(OH)D target values to DEQAS serum samples using their Joint Committee for Traceability in Laboratory Medicine (JCTLM) approved reference measurement procedure (RMP). Historically, NIST has performed 4 determinations of 25-OHD2 and 25-OHD3 on each sample and used the mean values to calculate a single ‘target value’ for Total 25-OHD against which performance was judged. By definition the target values cannot be exact and each is associated with a level of uncertainty. The total uncertainty (UNIST) has two components, one from the 25(OH)D2, and 25(OH)D3 measurements and the other associated with the calibration procedure. The total combined uncertainty is calculated by adding up these uncertainties. In future, uncertainties will be attached to the target value in each DEQAS serum sample, starting with the next distribution cycle in 2019. Confidence intervals obtained using these uncertainties will allow DEQAS participants to determine if their result agrees with the NIST assigned target value. Furthermore, if the value falls within the confidence interval the laboratory’s assay would be regarded as traceable, i.e. standardized, to the NIST RMP.

NUMBER: standardized reference intervals in the Netherlands using a 'big data' approach.

Background External quality assessment (EQA) programs for general chemistry tests have evolved from between laboratory comparison programs to trueness verification surveys. In the Netherlands, the implementation of such programs has reduced inter-laboratory variation for electrolytes, substrates and enzymes. This allows for national and metrological traceable reference intervals, but these are still lacking. We have initiated a national endeavor named NUMBER (Nederlandse UniforMe Beslisgrenzen En Referentie-intervallen) to set up a sustainable system for the determination of standardized reference intervals in the Netherlands. Methods We used an evidence-based 'big-data' approach to deduce reference intervals using millions of test results from patients visiting general practitioners from clinical laboratory databases. We selected 21 medical tests which are either traceable to SI or have Joint Committee for Traceability in Laboratory Medicine (JCTLM)-listed reference materials and/or reference methods. Per laboratory, per test, outliers were excluded, data were transformed to a normal distribution (if necessary), and means and standard deviations (SDs) were calculated. Then, average means and SDs per test were calculated to generate pooled (mean±2 SD) reference intervals. Results were discussed in expert meetings. Results Sixteen carefully selected clinical laboratories across the country provided anonymous test results (n=7,574,327). During three expert meetings, participants found consensus about calculated reference intervals for 18 tests and necessary partitioning in subcategories, based on sex, age, matrix and/or method. For two tests further evaluation of the reference interval and the study population were considered necessary. For glucose, the working group advised to adopt the clinical decision limit. Conclusions Using a 'big-data' approach we were able to determine traceable reference intervals for 18 general chemistry tests. Nationwide implementation of these established reference intervals has the potential to improve unequivocal interpretation of test results, thereby reducing patient harm.

Sources and performance criteria of uncertainty of reference measurement procedures

ObjectiveThis article wants to focus on the today available Reference Measurement Procedures (RMPs) for the determination of various analytes in Laboratory Medicine and the possible tools to evaluate their performance in the laboratories who are currently using them. MethodsA brief review on the RMPs has been performed by investigating the Joint Committee for Traceability in Laboratory Medicine (JCTLM) database. In order to evaluate their performances, we have checked the organization of three international ring trials, i.e. those regularly performed by the IFCC External Quality assessment scheme for Reference Laboratories in Laboratory Medicine (RELA), by the Center for Disease Control and Prevention (CDC) cholesterol network and by the IFCC Network for HbA1c. ResultsSeveral RMPs are available through the JCTLM database, but the best way to collect information about the RMPs and their uncertainties is to look at the reference measurement service providers (RMS). This part of the database and the background on how to listed in the database is very helpful for the assessment of expanded uncertainty (MU) and performance in general of RMPs. Worldwide, 17 RMS are listed in the database, and for most of the measurands more than one RMS is able to run the relative RMPs, with similar expanded uncertainties. As an example, for a-amylase, 4 SP offer their services with MU between 1.6 and 3.3%. In other cases (such as total cholesterol, the U may span over a broader range, i.e. from 0.02 to 3.6%). With regard to the performance evaluation, the approach is often heterogenous, and it is difficult to compare the performance of laboratories running the same RMP for the same measurand if involved in more than one EQAS. ConclusionsThe reference measurement services have been created to help laboratory professionals and manufacturers to implement the correct metrological traceability, and the JCTLM database is the only correct way to retrieve all the necessary important information to this end.

Comparison and bias estimation of isotope dilution mass spectrometry and HPLC for cholesterol: methodological comparison of two internationally accepted reference methods listed in JCTLM

Objective To evaluate the consistency and comparability of two kinds of cholesterol reference methods listed in the Joint Committee for Traceability in Laboratory Medicine (JCTLM). Methods 52 fresh frozen sera with cholesterol concentrations among 3-10 mmol/L were tested by isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS) and high performance liquid chromatography (HPLC). The precision and accuracy of the two methods were calculated, and then a series of analysis were conducted including plotting scatter plots and deviation graphs, testing outliers, selecting the best fitting regression models and calculating the regression equations and parameters, and so on. The results of the two methods were statistically analyzed to estimate the expected deviation at the level of medical decision of cholesterol and the 95% confidence range. Results For HPLC method, the CV of instrument measurement was 0.22% (0-0.49%), the total CV of samples measurement was 0.36% (0.02%-0.83%), and the average bias of the reference materials was 0.37% (-1.31%-0.14%). For ID-LC/MS/MS method, the CV of instrument measurement was 0.50% (0-1.51%), the total CV of samples measurement was 0.55% (0.03%-1.17%), and the average bias of the reference materials was 0.24% (-0.53%-0.14%). No outliers were found from the scatter plots and the statistical analysis and the linear regression were fitted to analyze the results of the two methods. The linear regression parameters of two methods for 52 fresh frozen human sera were as follows: the slope was 0.989 5, the standard error of slope was 0.003 4, the intercept was 0.063 4 mmol/L, the standard error of intercept was 0.019 9 mmol/L, the standard error of Y-estimate was 0.034 8 mmol/L, and the correlation coefficient was 0.999 7. Compared with the ID-LC/MS/MS method, the absolute deviation of fresh sera by HPLC method was 0.000 mmol/L (-0.083-0.076 mmol/L), with a relative deviation of 0.07% (-1.22-1.24%). T-test results showed no statistically significant difference between the two methods. The expected deviations at the cholesterol medicine decision level were within the range 95% confidence range, and the expected deviations were far less than the allowable error. Conclusions The HPLC method of cholesterol has good consistency and comparability with ID/MS method using the primary measurement principle. Because of more advantages of HPLC method such as less cost, more simple, requirement, and better precision, HPLC method is expected to play an important role in the process of standardization and traceability of serum cholesterol.(Chin J Lab Med, 2017, 40: 780-786) Key words: Cholesterol; Indicator dilution techniques; Chromatography, liquid; Tandem Mass spectrometry; Chromatography, high pressure liquid; Isotopes

Expressing analytical performance from multi-sample evaluation in laboratory EQA.

To provide its participants with an external quality assessment system (EQAS) that can be used to check trueness, the Dutch EQAS organizer, Organization for Quality Assessment of Laboratory Diagnostics (SKML), has innovated its general chemistry scheme over the last decade by introducing fresh frozen commutable samples whose values were assigned by Joint Committee for Traceability in Laboratory Medicine (JCTLM)-listed reference laboratories using reference methods where possible. Here we present some important innovations in our feedback reports that allow participants to judge whether their trueness and imprecision meet predefined analytical performance specifications. Sigma metrics are used to calculate performance indicators named 'sigma values'. Tolerance intervals are based on both Total Error allowable (TEa) according to biological variation data and state of the art (SA) in line with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Milan consensus. The existing SKML feedback reports that express trueness as the agreement between the regression line through the results of the last 12 months and the values obtained from reference laboratories and calculate imprecision from the residuals of the regression line are now enriched with sigma values calculated from the degree to which the combination of trueness and imprecision are within tolerance limits. The information and its conclusion to a simple two-point scoring system are also graphically represented in addition to the existing difference plot. By adding sigma metrics-based performance evaluation in relation to both TEa and SA tolerance intervals to its EQAS schemes, SKML provides its participants with a powerful and actionable check on accuracy.

Technical performance of a novel, fully automated electrochemiluminescence immunoassay for the quantitation of β-amyloid (1–42) in human cerebrospinal fluid

IntroductionAvailable assays for quantitation of the Alzheimer's disease (AD) biomarker amyloid-beta 1–42 (Aβ [1–42]) in cerebrospinal fluid demonstrate significant variability and lack of standardization to reference measurement procedures (RMPs). We report analytical performance data for the novel Elecsys β-amyloid (1–42) assay (Roche Diagnostics). MethodsLot-to-lot comparability was tested using method comparison. Performance parameters were measured according to Clinical & Laboratory Standards Institute (CLSI) guidelines. The assay was standardized to a Joint Committee for Traceability in Laboratory Medicine (JCTLM) approved RMP. ResultsLimit of quantitation was <11.28 pg/mL, and the assay was linear throughout the measuring range (200–1700 pg/mL). Excellent lot-to-lot comparability was observed (correlation coefficients [Pearson's r] >0.995; bias in medical decision area <2%). Repeatability coefficients of variation (CVs) were 1.0%–1.6%, intermediate CVs were 1.9%–4.0%, and intermodule CVs were 1.1%–3.9%. Estimated total reproducibility was 2.0%–5.1%. Correlation with the RMP was good (Pearson's r, 0.93). DiscussionThe Elecsys β-amyloid (1–42) assay has high analytical performance that may improve biomarker-based AD diagnosis.

A candidate reference method using ICP-MS for sweat chloride quantification

The aim of the study was to develop a method for sweat chloride (Cl) quantification using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to present to the Joint Committee for Traceability in Laboratory Medicine (JCTLM) as a candidate reference method for the diagnosis of cystic fibrosis (CF). Calibration standards were prepared from sodium chloride (NaCl) to cover the expected range of sweat Cl values. Germanium (Ge) and scandium (Sc) were selected as on-line (instrument based) internal standards (IS) and gallium (Ga) as the off-line (sample based) IS. The method was validated through linearity, accuracy and imprecision studies as well as enrolment into the Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP) for sweat electrolyte testing. Two variations of the ICP-MS method were developed, an on-line and off-line IS, and compared. Linearity was determined up to 225 mmol/L with a limit of quantitation of 7.4 mmol/L. The off-line IS demonstrated increased accuracy through the RCPAQAP performance assessment (CV of 1.9%, bias of 1.5 mmol/L) in comparison to the on-line IS (CV of 8.0%, bias of 3.8 mmol/L). Paired t-tests confirmed no significant differences between sample means of the two IS methods (p=0.53) or from each method against the RCPAQAP target values (p=0.08 and p=0.29). Both on and off-line IS methods generated highly reproducible results and excellent linear comparison to the RCPAQAP target results. ICP-MS is a highly accurate method with a low limit of quantitation for sweat Cl analysis and should be recognised as a candidate reference method for the monitoring and diagnosis of CF. Laboratories that currently practice sweat Cl analysis using ICP-MS should include an off-line IS to help negate any pre-analytical errors.

An approach to establish the uncertainty budget of catalytic activity concentration measurements in a reference laboratory.

Reference laboratories providing reference services recognized by the Joint Committee for Traceability in Laboratory Medicine (JCTLM) must be accredited as calibration laboratories according to ISO 17025 and ISO 15195. These standards require laboratories to establish an uncertainty budget, in which the uncertainty contributions of the relevant uncertainty components are specified. We present a model to estimate the measurement uncertainty of creatine kinase catalytic activity concentration results obtained by IFCC primary reference measurement procedure. The measurement uncertainty has been estimated by following the next steps: 1) specification of the measurand; 2) identification of the most relevant uncertainty sources; 3) estimation of standard uncertainties by either type A or type B evaluation; 4) estimation of combined uncertainty while taking into account sensitivity coefficients, as well as existence of correlated uncertainty sources; and 5) estimation of expanded uncertainty with a defined coverage probability. The estimated expanded uncertainty was 2.2% (k=2). Uncertainty sources with a significant contribution to the measurement uncertainty were the following: pH adjustment (0.68%), absorbance accuracy (0.48%), wavelength adjustment (0.20%), reaction temperature (0.19%), volume fraction of sample (0.15%) and absorbance linearity (0.06%). The present model is an approach to establish the uncertainty budget of primary reference procedures for the measurement of the catalytic activity concentration of enzymes, and aims at being an example to be followed by other reference laboratories, as well as by laboratories that carry out primary reference measurement procedures.

System Accuracy Evaluation for Blood Glucose Measurements Should Be Performed in Accordance with ISO 15197:2003 and CLSI-Approved Guideline EP7-A2

Dear Editor: Warner et al.1 recently reported potential risks to patient welfare with the use of bedside rather than laboratory blood glucose (bG) measurement on bG meters such as the Accu-Chek® Performa (Roche Diagnostics, Mannheim, Germany). Warner et al.1 are claiming that this bG meter potentially fails to diagnose hypoglycemia and might lead to overtreatment of hyperglycemia in patients with high blood maltose concentrations and high hematocrit values. Our review of their methods identified several key discrepancies that may help to explain their conclusions. First, the manufacturer's recommended comparison method of the Accu-Chek Performa bG meter is the hexokinase method with deproteinization of capillary whole blood samples. This hexokinase method is directly calibrated to the reference measurement procedure isotope dilution gas chromatography/mass spectrometry (ID-GC/MS), which is a reference procedure recommended by the Joint Committee for Traceability in Laboratory Medicine (JCTLM)2 (JCTLM DB identification number: C3RMMP19, isotope dilution mass spectrometry method for glucose in whole blood). The Vitros 5,1 FS (Ortho Clinical Diagnostics, Raritan, NJ) glucose method against which Warner et al.1 did compare the Accu-Chek Performa is a glucose oxidase–peroxidase method using plasma. Use of the Vitros 5,1 FS as a comparison method is not in accordance with the recommendation of the International Organization for Standardization (ISO) 15197:2003,3 which requires that bG meters are being evaluated by the comparison method recommended by the manufacturer or by another validated measurement procedure that has been shown to produce equivalent results. The Vitros 5,1 FS glucose method is not the comparison method that has been recommended by Roche. In addition, the glucose measurement on a clinical chemical analyzer is associated with a measurement error. As we know from external quality assessment schemes (EQAS), the variation of glucose measurement values between different clinical chemical analyzers can be significant. An example is that the (German) Referenzinstitut fur Bioanalytik publishes EQAS results with open access to the public on its website. A sample from a recent EQAS (May 2, 2011) with a glucose reference value (determined by ID-GC/MS) of 76.6 mg/dL had an inter-laboratory coefficient of variation of 5.95%.4 The authors would have had to run the Vitros 5,1 FS glucose method and the method recommended by Roche side by side to prove equivalence. It is nowhere indicated in their publication that they did so. Furthermore, ISO 15197:2003 requires that the system accuracy evaluation shall be performed with at least 100 fresh capillary blood samples, each with sufficient volume to be measured by two different bG meters and at least in duplicate by the manufacturer's recommended measurement procedure. The study from Warner et al.1 provides information about only 40 samples with no further details supporting the conclusions made by the authors. Second, data for maltose mentioned in the publication of Warner et al.1 are based on a pharmacodynamic modeling calculation published by Schleis,5 which yielded a theoretical maximum maltose concentration of 2,650 mg/dL (77 mmol/L). The calculation is based on two assumptions: (1) that no maltose is converted during the infusion process and (2) that the infusion is essentially instantaneous. To date, the concentration of 2,650 mg/dL maltose has never been observed in real-life patients. Assuming a maltose concentration of 600 mg/dL (17.5 mmol/L), which is the maximum that has been observed in an analysis of six real-life infusion experiments by Schleis,5 would change the true glucose value of 39.6 mg/dL (2.2 mmol/L) to 54.0 mg/dL (3.0 mmol/L) as shown by Warner et al.6 This would not lead to inappropriate treatment. Third, according to the guideline of the Clinical and Laboratory Standards Institute (CLSI) for interference testing in clinical chemistry,7 it is necessary for the assessment of an interferent such as hematocrit to compare samples with the same glucose concentration and different hematocrit values with each other only on the same instrument. This procedure isolates the effect of the interferent, while any comparison to a different instrument results in a deviation that is not only due to the interferent but also partly due to the measurement error of the different instrument. The hematocrit figures in the publication of Warner et al.1 showed glucose concentrations at different hematocrit concentrations that were measured with the Accu-Chek Performa and then compared with the corresponding values measured with the Vitros 5,1 FS. If Warner et al.1 had followed the CLSI guideline for interference testing, the observed deviation would have been much smaller and would then lead to a different assessment. In summary, in our opinion it can therefore be stated that the conclusions in Warner at al.1 regarding the maltose interference and the putative evidence of a positive bias at higher hematocrit values with the Accu-Chek Performa are not supported because of the fact that the experiments have not been performed according to the ISO 15197:2003 standard3 and the CLSI guideline for interference testing.7

Bilirubin Standardization in the Netherlands: Alignment within and between Manufacturers

In 2008, two manufacturers lowered the values of their bilirubin calibrators: Abbott Laboratories by 18% and Roche by 10%–17% (different values per instrument). Beckman Coulter, Siemens/Bayer, and Siemens/Dade Behring did not restandardize their methods. In 2009, the Dutch External Quality Assessment Organization in Medical Laboratories [Stichting Kwaliteitsbewaking Medische Laboratoria (SKML)1 ] investigated the impact on the mean measured concentration and the interlaboratory variation of assays for total bilirubin. Pooled human serum was supplemented with unconjugated bilirubin (>99%; Bilirubin, Mixed isomers; Sigma-Aldrich). Serum samples were dispensed, frozen below −70 °C, and shipped on dry ice to the participating laboratories in the regular external quality-assessment program of February 2009. Mean target values were 26.7 μmol/L (95% CI, 26.1–27.3 μmol/L) and 68.7 μmol/L (95% CI, 67.2–70.2 μmol/L), as assigned with the Doumas reference measurement procedure(1)(2)(3) in the Joint Committee for Traceability in Laboratory Medicine (JCTLM)-listed reference laboratory in Hanover, Germany. The manufacturers also analyzed the samples in house with their respective routine methods. This design allowed a direct comparison of the results from routine laboratories and manufacturers’ in-house results with the target values assigned by the reference method. Fig. 1⇓ shows the results submitted by 183 routine laboratories, …

International Activities in Metrology in Chemistry

In today's economy goods and information are being exchanged globally, international travel is commonplace as is the cross-boarder transport of livestock and agricultural products, and this trend is set to continue. Just as important are issues that impinge on our quality of life, such as health care, the environment and food quality. A strong international measurement and standards infrastructure is critical to assure equity in trade and a high quality of life, by ensuring that products and services meet their specifications. In the field of chemical measurements, certified reference materials (CRMs), measurement standards and reference measurement results provide stated references upon which analytical laboratories can anchor their measurement results. The traceability of measurement results to internationally accepted stated references, together with their stated measurement uncertainties, as described in ISO/IEC 17025, provides the basis for their comparability and global acceptance. Recent global activities which are succeeding in developing a system for the international acceptance of chemical measurements are described, notably: activities of the National Metrology Institutes and the BIPM; the Mutual Recognition Arrangement of the International Committee of Weights and Measures (CIPM MRA) for National Calibration Certificates and Measurement Capabilities; the Inter-Laboratory Comparisons organised through the working groups of the Consultative Committee for Amount of Substance – Metrology in Chemistry (CCQM), and the activities of the Joint Committee for Traceability in Laboratory Medicine (JCTLM).

Proposal of a candidate international conventional reference measurement procedure for free thyroxine in serum

In the present paper the IFCC WG-STFT recommends and provides the rationale to establish metrological traceability of serum free thyroxine (FT4) measurements to a candidate international conventional reference measurement procedure. It is proposed that this procedure be based on equilibrium dialysis combined with determination of thyroxine in the dialysate with a trueness-based reference measurement procedure. The measurand is thus operationally defined as "thyroxine in the dialysate from equilibrium dialysis of serum prepared under defined conditions". With regard to the trueness-based reference measurement procedure, the WG-STFT recommends use of an isotope dilution-liquid chromatography/tandem mass spectrometry (ID-LC/tandem MS) procedure for total thyroxine that has been optimized towards measurement at picomolar concentration levels and that is listed in the database of the Joint Committee for Traceability in Laboratory Medicine (JCTLM). For calibration, the purified thyroxine material IRMM-468 (resulting from a project funded by the European Commission and recently submitted to the JCTLM) is proposed. The WG-STFT stresses that according to this recommendation it is a prerequisite to strictly adhere to the defined equilibrium dialysis procedure, whereas it is permissible to introduce variants in the ID-LC/tandem MS procedure.