Final report on CCQM-K80: Comparison of value-assigned CRMs and PT materials: Creatinine in human serum

Abstract

The 2009 CCQM-K80 'Comparison of value-assigned CRMs and PT materials: creatinine in human serum' is the first in a series of key comparisons directly testing the chemical measurement services provided to customers by National Metrology Institutes (NMIs) and Designated Institutes. CCQM-K80 compared the assigned serum creatinine values of certified reference materials (CRMs) using measurements made on these materials under repeatability conditions. Six NMIs submitted 17 CRM materials for evaluation, all intended for sale to customers. These materials represent nearly all of the higher-order CRMs then available for this clinically important measurand.The certified creatinine mass fraction in the materials ranged from 3 mg/kg to 57 mg/kg. All materials were stored and prepared according the specifications provided by each NMI. Samples were processed and analyzed under repeatability conditions by one analyst using isotope dilution liquid chromatography–mass spectrometry. The instrumental repeatability imprecision, expressed as a percent relative standard deviation, was 1.2%.Given the number of materials and the time required for each analysis, the measurements were made in two measurement campaigns ('runs'). In both campaigns, replicate analyses (two injections of one preparation separated in time) were made on each of two or three independently prepared aliquots from one randomly selected unit of each of the 17 materials. The mean value, between-campaign, between-aliquot and between-replicate variance components, standard uncertainty of the mean value, and the number of degrees of freedom associated with the standard uncertainty were estimated using a linear mixed model. Since several of the uncertainties estimated using this traditional frequentist approach were associated with a single degree of freedom, Markov Chain Monte Carlo Bayesian analysis was used to estimate 95% level-of-confidence coverage intervals, U95. Uncertainty-weighted generalized distance regression was used to establish the key comparison reference function (KCRF) relating the assigned values to the repeatability measurements. Parametric bootstrap Monte Carlo was used to estimate 95% level-of-confidence coverage intervals for the degrees of equivalence of materials, d ± U95(d), and of the participating NMIs, D ± U95(D). Because of the wide range of creatinine mass fraction in the materials, these degrees of equivalence are expressed in percent relative form: %d ± U95(%d) and %D ± U95(%D).On the basis of leave-one-out cross-validation, the assigned values for 16 of the 17 materials were deemed equivalent at the 95% level of confidence. These materials were used to define the KCRF. The excluded material was identified as having a marginally underestimated assigned uncertainty, giving it large and potentially anomalous influence on the KCRF. However, this material's %d of 1.4 ± 1.5 indicates that it is equivalent with the other materials at the 95% level of confidence. The median |%d| for all 17 of the materials is 0.3 with a median U95(%d) of 1.9. All of these higher-order CRMs for creatinine in human serum are equivalent within their assigned uncertainties.The median |%D| for the participating NMIs is 0.3 with a median U95(%D) of 2.1. These results demonstrate that all participating NMIs have the ability to correctly value-assign CRMs and proficiency test materials for creatinine in human serum and similar measurands.Main text.To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).