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Exploring commutable materials for serum folate measurement: challenges in cross-method harmonization

  • Xiaerbanu Nizhamuding , Qian Zhang , Lizi Jin , Rui Wu , Youli Lu , Xilian Yi , Meiwei Zhang , Jiangtao Zhang , Weiyan Zhou , Jie Zeng , Tianjiao Zhang EMAIL logo and Chuanbao Zhang ORCID logo EMAIL logo
Published/Copyright: June 26, 2025
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 11

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.

Keywords: serum folate; commutability; external quality assessment; reference materials; immunoassays; LC-MS/MS
Corresponding authors: Tianjiao Zhang, MD and Chuanbao Zhang, National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology, No. 1 Dahua Road, Dongcheng District, Beijing 100730, P.R. China; and Chinese Academy of Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China, E-mail: (T. Zhang), (C. Zhang)
Xiaerbanu Nizhamuding and Qian Zhang contributed equally to this work.

Funding source: National Key Research and Development progrem of China

Award Identifier / Grant number: No. 2022YFF0710305

Funding source: National High Level Hospital Clinical Research Funding

Award Identifier / Grant number: BJ-2023-106

Acknowledgments

The sera collected from Beijing Hospital and used in this study were also employed in our previous work (Jin et al. [13]). The overlap in the data serves solely to illustrate the performance of the method. The study materials have not been published elsewhere and are exclusively used in this research. We’re grateful for the support and technical guidance of engineers of Abbott, Roche, Beckman.

  1. Research ethics: This retrospective study was approved by the Ethics Committee of Beijing Hospital.

  2. Informed consent: This study was approved for the exemption from informed consent.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: National Key Research and Development Program of China (No. 2022YFF0710305); National High Level Hospital Clinical Research Funding (BJ-2023-106).

  7. Data availability: The raw data can be obtained on request from the corresponding author.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2024-1403).

Received: 2024-12-02
Accepted: 2025-06-02
Published Online: 2025-06-26
Published in Print: 2025-10-27

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2024-1403
Keywords for this article
serum folate; commutability; external quality assessment; reference materials; immunoassays; LC-MS/MS

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Advancing diagnostic stewardship through claims-based utilization analysis: toward a system-wide vision of diagnostic excellence
  4. Review
  5. Biomarkers in body fluids and their detection techniques for human intestinal permeability assessment
  6. Mini Review
  7. Challenges of using natriuretic peptides to screen for the risk of developing heart failure in patients with diabetes: a report from the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Committee on Clinical Applications of Cardiac Bio-Markers (C-CB)
  8. Opinion Papers
  9. Reference intervals in value-based laboratory medicine: a shift from single-point measurements to metabolic variation-based models
  10. Overview of laboratory diagnostics for immediate management of patients presenting to the emergency department with acute bleeding
  11. What Matters Most: an Age-Friendly approach to pathology and laboratory medicine
  12. No fault or negligence after an adverse analytical finding due to a contaminated supplement: mission impossible. Two examples involving trimetazidine
  13. General Clinical Chemistry and Laboratory Medicine
  14. Utilization analysis of laboratory tests using health insurance claims data: advancing nationwide diagnostic stewardship monitoring systems
  15. Evaluating large language models as clinical laboratory test recommenders in primary and emergency care: a crucial step in clinical decision making
  16. A novel corrective model based on red blood cells indices and haemolysis index enables accurate unhaemolysed potassium determination in haemolysed samples – Hemokalc project
  17. Validation of (self-collected) capillary blood using a topper collection system as alternative for venous sampling for 15 common clinical chemistry analytes
  18. Acoustophoresis-based blood sampling and plasma separation for potentially minimizing sampling-related blood loss
  19. Clinical validation of a liquid chromatography single quadrupole mass spectrometry (LC-MS) method using Waters Kairos™ Amino Acid Kit reagents
  20. Robustness of steroidomics-based machine learning for diagnosis of primary aldosteronism: a laboratory medicine perspective
  21. Investigation of the possible cause of over-estimation of human aldosterone in plasma, using a unique, non-synthetic human aldosterone-free matrix
  22. Performance of afternoon (16:00 h) serum cortisol for the diagnosis of Cushing’s syndrome
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  24. Assessment of 2023 ACR/EULAR antiphospholipid syndrome classification criteria in a Spanish cohort
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