Exploring commutable materials for serum folate measurement: challenges in cross-method harmonizationXiaerbanu Nizhamudingon June 25, 2025 at 10:00 am

Clin Chem Lab Med. 2025 Jun 26. doi: 10.1515/cclm-2024-1403. Online ahead of print.

ABSTRACT

OBJECTIVES: Commutability is a critical attribute for reference materials (RMs) employed in standardization and calibration activities, it ensures the accuracy and equivalence of analytical results across heterogeneous measurement systems and laboratories. In the context of folate quantification, commutability holds particular significance, as it validates that RMs exhibit analytical behavior equivalent to native clinical specimens when subjected to diverse folate detection platforms. This study aims to identify and characterize commutable candidate RMs for serum folate assays, with the ultimate goal of enhancing the harmonization and metrological traceability of folate measurements in clinical diagnostics.

METHODS: Thirty study materials and pooled clinical serum samples were measured by two isotope-dilution liquid chromatography tandem mass spectrometry methods and three immunoassays in four different laboratories. Six external quality assessment materials for endocrine, 6 trueness verification materials for vitamins, 13 processed materials and 5 candidate RMs (cRM-1,2,3,4,5) were assessed. Deming regression analysis and the difference-in-bias approach were employed to evaluate commutability.

RESULTS: cRM-3 demonstrated commutability (C or +) across all assays, being the most ideal candidate reference material in this study. Seven materials (cRM-1, cRM-2, cRM-3, TV202111, TV202012, CS-L, and RS 2W-1) were commutable for two LC-MS/MS methods regardless of the statistical method.

CONCLUSIONS: The complexity of folate species in serum, differences in detection principles between immunoassays and isotope-dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method (immunoassays using folate-binding protein with variable affinities and LC-MS/MS quantifying specific vitamers), and variations in calibration substrates among immunoassays collectively challenge the harmonization of folate measurement and commutability assessment.

PMID:40560660 | DOI:10.1515/cclm-2024-1403

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