Commutable whole blood reference materials for hemoglobin A1c validated on multiple clinical analyzers.

Background: The measurement of hemoglobin A(1c) (HbA(1c)) is important for diagnosing diabetes mellitus as well as assessing glycemic control in diabetic patients. Commutable whole blood certified reference materials (CRMs) are needed in the measurement of HbA(1c) for method validation and/or as quality controls. Methods: We developed three levels of hemolyzed whole blood CRMs for HbA(1c). The certified values were determined using liquid chromatography-isotope dilution tandem mass spectrometry method (LC-IDMS/MS) where two "signature" hexapeptides of HbA(1c) and hemoglobin A(0) (HbA(0)) were used as the calibration standards. The concentrations of the hexapeptide solutions were determined by amino acid analysis by the LC-IDMS/MS method using amino acid CRMs as the calibration standards. The commutability study was conducted by measuring 25 patient specimens and the whole blood CRMs by both LC-IDMS/MS method and various routine methods using six different clinical analyzers. Results: The certified values were determined to be 35.1 +/- 2.0, 50.3 +/- 1.9 and 65.8 +/- 2.6 mmol/mol, respectively. These CRMs showed good commutability on five of the six clinical analyzers but showed poor commutability on one of the clinical analyzers that used similar method as two other analyzers where good commutability was observed. Conclusions: With certified target values based on metrological traceability and good commutability on most of the clinical analyzers, the developed whole blood CRMs can be used for method validation or as quality control materials in the measurement of HbA(1c). The commutability study results also underscored the need of commutability testing of clinical CRMs using various clinical analyzers.