University of Oulu

Berry, D. J., Dutton, J., Fraser, W. D., Järvelin, M.-R. and Hyppönen, E. (2017), Harmonization Study Between LC-MS/MS and Diasorin RIA for Measurement of 25-Hydroxyvitamin D Concentrations in a Large Population Survey. J. Clin. Lab. Anal., 31: n/a, e22049. doi:10.1002/jcla.22049

Harmonization study between LC-MS/MS and diasorin RIA for measurement of 25-hydroxyvitamin D concentrations in a large population survey

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Author: Berry, Diane J.1; Dutton, John2; Fraser, William D.3;
Organizations: 1Population, Policy and Practice, UCL Institute of Child Health, London, UK
2Department of Clinical Biochemistry, Royal Liverpool University Hospital, Liverpool, UK
3Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, UK
4Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK
5Unit of Primary Care, Oulu University Hospital, Oulu, Finland
6Department of Children, Young People and Families, National Institute for Health and Welfare, Oulu, Finland
7Biocenter Oulu, Institute of Health Sciences, University of Oulu, Oulu, Finland
8Centre for Population Health Research, School of Health Sciences and Sansom Institute of Health Research, University of South Australia, Adelaide, Australia
9South Australian Health and Medical Research Institute, Adelaide, Australia
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.5 MB)
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Language: English
Published: John Wiley & Sons, 2017
Publish Date: 2017-07-05


Background: Population-based research on vitamin D has increased dramatically in recent years. Such studies are typically reliant on assay procedures to measure reliable and comparable levels of 25-hydroxyvitamin D [25(OH)D] concentrations.

Methods: Concentrations of 25(OH)D₃ and 25(OH)D₂ were measured using LC-MS/MS in 5,915 participants (aged 31 years) of Northern Finland Birth Cohort 1966. Blood samples were assayed in batches over a course of 18 months. As anomalies were present in the measurements, 200 samples were reassayed using Diasorin RIA. Agreement between measurements was assessed by Passing–Bablok regression and limits of agreement (LoA). To harmonize LC-MS/MS with Diasorin RIA measurements, formulae were derived from the LoA.

Results: Concentrations measured by LC-MS/MS were much higher than those measured by Diasorin RIA, with a mean difference of 12.9 ng/ml. Constant variation was evident between batch measurements after log transformation. Statistical formula was applied separately for each batch of LC-MS/MS measurements, enabling us to remove both the constant and proportional bias that was evident prior to the transformation.

Conclusion: Despite the introduction of schemes/programs to improve accuracy of assays to measure 25(OH)D, significant differences can still happen. In these instances, methods to harmonize measurements based on a relatively small number of replicates can be successfully applied to establish confidence and to enable between-study comparisons.

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Series: Journal of clinical laboratory analysis
ISSN: 0887-8013
ISSN-E: 1098-2825
ISSN-L: 0887-8013
Volume: 31
Issue: 3
Article number: e22049
DOI: 10.1002/jcla.22049
Type of Publication: A1 Journal article – refereed
Field of Science: 314 Health sciences
Funding: Funding for the project was provided by the UK Medical Research Council (grant G0601653). The NFBC1966 is financially supported by the Academy of Finland (project grants 24300796, 12926), University Hospital Oulu, Biocenter, University of Oulu, Finland (75617), and the Medical Research Council, UK (PrevMetSyn/ SALVE). Research at the University College London Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from R&D funding received from the NHS Executive.
Copyright information: © 2016 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.