Development of an isotope dilution gas chromatography - mass spectrometry candidate reference measurement procedure for glucose in human serum.

INTRODUCTION: Diabetes is the seventh leading cause of death in the United States, impacting over 37 million people. Accurate glucose measurements are critical for effective diabetes management. A reliable candidate reference measurement procedure (cRMP) for assessing the analytical performance of glucose tests performed in patient care is essential for ensuring measurement accuracy. METHODS: We have developed a gas chromatography-mass spectrometry (GC-MS)-based cRMP for glucose in human serum. In this procedure, glucose is measured as the aldononitrile acetate derivative and quantitated using a (13)C(6)-glucose internal standard. RESULTS: Analytical selectivity was achieved through chromatographic separation and monitoring the quantitation ion/confirmation ion ratios in samples. With bias ranging from -0.79 % to 0.67 % for eight levels of serum-based certified reference materials from the National Institute of Standards and Technology (NIST) and Laboratoire national de métrologie et d'essais (LNE) and total CVs of 1.11 %, 0.68 % and 0.74 % at the low, medium, and high glucose concentration levels, respectively, the cRMP provided excellent accuracy and precision. The calibration curve was linear throughout the 13.51-378.21 mg/dL [0.75-21 mmol/L] measurement range (R(2) = 0.9999), with a mean slope of 270.73 (95 % CI, 270.19 to 271.27) and an intercept of 0.021 (95 % CI, -0.157 to 0.199). The limit of detection was 0.25 mg/dL (0.014 mmol/L) and the limit of quantitation was 0.83 mg/dL (0.046 mmol/L). CONCLUSION: The described GC-MS method, with metrological traceability to the International System of Units (SI), provides highly accurate and precise measurements of glucose in human serum.