Development of an isotope dilution gas chromatography - mass spectrometry candidate reference measurement procedure...

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.

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 ¹³C₆-glucose internal standard.

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 (R² = 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).

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.