Background: Serum C-peptide concentrations reflect pancreatic function in different clinical and diagnostic settings; however, the utility of C-peptide testing is limited by the lack of standardized commercial immunoassays. Standardization can best be done by splitsample comparison with a hierarchically higher reference measurement procedure with a set of native sera. For serum peptides, isotope-dilution liquid chromatography-mass spectrometry (ID-LC/MS) is recommended as a reference measurement procedure. Methods: We evaluated the analytical performance characteristics of an ID-LC/tandem MS procedure for measurement of serum C-peptide after a 2-step solidphase extraction. To investigate the feasibility of this procedure for use in standardization, we also performed a method comparison with 3 representative commercial assays. Results: The ID-LC/tandem MS procedure showed maximum within-run, between-run, and total CVs on dedicated sera (C-peptide concentrations, 1.6 and 4.0 g/L) of 2.1%, 2.5%, and 2.9%, respectively; an accuracy of 94.6%-104.1%; a minimum trueness of 98.1% (95% confidence interval, 96.2%-100.0%), and limits of quantification and detection of 0.15 and 0.03 g/L, respectively. Deming linear regression analysis of the method-comparison data showed that the immunoassays correlated well with ID-MS and were specific, but lacked intercomparability and trueness. We propose that the deficiencies can be resolved by recalibration on the basis of the method comparison. Conclusions: The ID-LC/tandem MS procedure is suitable for specific and accurate measurement of basal and stimulated serum concentrations of proinsulin C-peptide fragment 33-63 and is suitable for use in standardization of C-peptide immunoassays.
This manuscript explains the establishment and validation of metrological traceability of calibration for routine measurement procedures using common medical decision-making criteria. Metrological traceability is considered the basis for achieving comparability of measurement results in laboratory medicine. This concept is supported by European legislation, which demands that manufacturers provide assurance and demonstrate metrological traceability of in vitro Diagnostic Medical Devices. The guidance to comply with these legislative requirements is available in different CEN/ISO standards and is used as a basis of this manuscript. The goals and accomplishments in metrological traceability of SI- and non-SI analytes is considered. Specific problems, such as non-availability of primary reference materials and measurement procedures, lack of official endorsement, and non-commutability of certain reference materials are discussed. With respect to non-commutability, the use of split-sample measurements is advocated. Also, the expression of measurement uncertainty associated with the application of the metrological traceability chain is discussed. In addition, the need for post-market vigilance assessment of traceable performance is considered. Finally, laboratory medicine scientific and professional societies, diagnostics manufacturers, and clinicians are urged to share responsibilities for understanding the implications of metrological traceability of routine measurements.
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