Metrologic traceability of total thyroxine measurements in human serum: efforts to establish a network of reference measurement laboratories.
BACKGROUND
Assuring/demonstrating metrologic traceability of in vitro diagnostics necessitates the availability of measurand-specific reference measurement systems (RMSs) and the possibility for industry to work with competent reference measurement laboratories (RMLs). Here we report the results of a European project to investigate the feasibility of developing a RMS for serum total thyroxine.


METHODS
Four candidate RMLs (cRMLs) developed/implemented variants of a candidate reference measurement procedure (cRMP) based on isotope dilution-liquid chromatography-mass spectrometry. The sole constraint implemented was calibration with a common thyroxine primary calibrator. The RMPs were externally validated and assessed for comparability in round-robin trials using common samples, i.e., 5 lyophilized and 33 frozen native sera. At the same time, the performance of the cRMLs organized in a network was assessed. For uniform external quality assessment, common performance specifications were agreed on.


RESULTS
All cRMLs performed the cRMPs with fulfillment of the predefined specifications: total and between-laboratory CVs < or =2.0% and 2.5%, respectively, and a systematic deviation < or =0.9%, estimated with a target assigned from the mean of means obtained by the cRMLs. The mean expanded uncertainty for value assignment to the native sera was 2.1%.


CONCLUSIONS
A network of cRMLs, with externally conformed competence to properly perform RMPs, has been established. Performance specifications were defined and will form the basis for admittance of new network members. A serum panel, successfully targeted during the validation process, is available for split-sample measurements with commercial routine measurement procedures. The model can now be used for other measurands for which traceability to the Systeme International d'Unites is needed.
Thienpont
Linda M
LM
Laboratory for Analytical Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Gent, Belgium. linda.thienpont@ugent.be
Van Uytfanghe
Katleen
K
Marriot
John
J
Stokes
Peter
P
Siekmann
Lothar
L
Kessler
Anja
A
Bunk
David
D
Tai
Susan
S
D002853:Chromatography, Liquid; D019411:Clinical Laboratory Techniques / Q000592:standards*; D005240:Feasibility Studies; D006801:Humans; D007201:Indicator Dilution Techniques; D007753:Laboratories / Q000458:organization & administration*; D013058:Mass Spectrometry; D012015:Reference Standards; D015203:Reproducibility of Results; D044967:Serum; D013974:Thyroxine / Q000097:blood* / Q000592:standards
D013974:Thyroxine