Pilot study for the standardization of insulin immunoassays with isotope dilution liquid chromatography/tandem mass spectrometry.

BACKGROUND: An international working group convened by the American Diabetes Association (ADA) called for a reference measurement procedure for use in a trueness-based standardization project of insulin immunoassays. In view of this demand, we conducted a pilot study to investigate the feasibility of such a standardization project with our isotope dilution-liquid chromatography/tandem mass spectrometry (ID-LC/tandem MS) procedure. METHODS: We evaluated the precision, accuracy, and limit of quantification (LoQ) of the ID-LC/tandem MS procedure by use of insulin-free serum supplemented with insulin to give 3 pools with concentrations of 0.0796, 0.769, and 5.56 microg/L. We conducted a pilot method comparison study with 4 immunoassays and 80 samples from fasting and glucose-stimulated patients. RESULTS: The within-run and total imprecision (CV) ranged from 3.2% to 6.3% and from 4.9% to 12.1% (listing sequence from the high to the low pool). The recovery from supplemented insulin-free sera ranged from 101.8% to 104.1%, and the LoQ was 0.07 microg/L (12 pmol/L). Weighted Deming regression and correlation analysis of the method-comparison data showed considerable between-assay variation for the immunoassays but, with the exception of one assay, excellent correlation with ID-LC/tandem MS. Recalibration of the immunoassay results considerably reduced the between-assay variation. Moreover, after recalibration, 3 of the 4 assays fulfilled the total error specification of 32% proposed by the ADA Workgroup. CONCLUSIONS: Recalibration of insulin assays by regression equations established from method comparison with ID-LC/tandem MS can result in successful standardization and fulfillment of the total error criterion proposed by the ADA Workgroup.

Metrological traceability of calibration in the estimation and use of common medical decision-making criteria.

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.