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Vitamin D Assays: Past And Present Debates, Difficulties, And Developments

W. Fraser, A. M. Milan
Published 2012 · Chemistry, Medicine

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Clinical interest in Vitamin D and its purported roles not only in calcium and bone metabolism but in several other medical conditions (diabetes, cardiovascular disease, multiple sclerosis, cancer, psychiatric disorders, neuro-muscular disease) has led to a surge in laboratory requests for 25 hydroxy vitamin D and 1,25 dihydroxy vitamin D measurement. Circulating 25 hydroxy vitamin D concentration is routinely used as the best indicator of vitamin D status, but measurement of other metabolites, especially the physiologically active 1,25 dihyroxy vitamin D, are of clinical value. Over the last 40 years the development of assays for vitamin D and its metabolites from early competitive binding assays through to immunoassay and liquid chromatography aligned to mass spectrometry have demonstrated various analytical challenges, the advantages and disadvantages of each method are constantly changing with new technological developments. Immunoassay remains the predominant mode of measurement for 25-hydroxy vitamin D although problems with equimolar recovery of the D2 and D3 metabolites remain an issue. Standardisation of all assays has been improved but not resolved with the currently available reference materials as evidenced by the international vitamin D external quality assurance scheme, DEQAS. The choice of method for each laboratory remains a balance mainly between turn around time, convenience, cost and the specificity and accuracy of the information obtained. With increasing discussion and clinical interest surrounding other vitamin D metabolites the vitamin D assay debate is set to continue.
This paper references
10.1016/0021-9673(93)80625-I
Characterization of vitamin D3 metabolites using continuous-flow fast atom bombardment tandem mass spectrometry and high-performance liquid chromatography.
B. Yeung (1993)
10.1021/ac9026862
Development of a candidate reference measurement procedure for the determination of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 in human serum using isotope-dilution liquid chromatography-tandem mass spectrometry.
S. Tai (2010)
High-performance liquid chromatographic assay for 25-hydroxyvitamin D 3 in serum
Tj Gilbertson (1977)
10.1016/j.clinbiochem.2012.01.021
Analytical evaluation of the new Abbott Architect 25-OH vitamin D assay.
E. Cavalier (2012)
10.1016/j.cca.2008.01.017
Measurement of 25-hydroxyvitamin D3 (25OHD3) and 25-hydroxyvitamin D2 (25OHD2) in human serum using liquid chromatography-tandem mass spectrometry and its comparison to a radioimmunoassay method.
H. Chen (2008)
10.1016/j.cca.2010.08.018
Current status of clinical 25-hydroxyvitamin D measurement: an assessment of between-laboratory agreement.
N. Binkley (2010)
10.1016/S0009-9120(02)00378-8
Analytical and clinical validation of a radioimmunoassay for the measurement of 1,25 dihydroxy vitamin D.
Diana R Clive (2002)
10.1093/clinchem/22.3.364
Measurement of 25-hydroxyvitamin D3 in serum.
R. Bouillon (1976)
10.1373/clinchem.2010.161174
Quantification of 1α,25-dihydroxy vitamin D by immunoextraction and liquid chromatography-tandem mass spectrometry.
Frederick G. Strathmann (2011)
10.1093/clinchem/26.5.0562
A radioimmunoassay for 1,25-dihydroxycholecalciferol.
T. Clemens (1978)
Serum vitamin D 2 and vitamin D 3 metabolite concentrations and absorption of vitamin D 2 in elderly subjects
Tl Clemens (1986)
10.1016/j.cca.2011.05.010
Isotope dilution ultra performance liquid chromatography-tandem mass spectrometry method for simultaneous measurement of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3 and 3-epi-25-hydroxyvitamin D3 in human serum.
R. Schleicher (2011)
10.1093/CLINCHEM/46.10.1657
Comparison of commercially available (125)I-based RIA methods for the determination of circulating 25-hydroxyvitamin D.
B. Hollis (2000)
10.1258/acb.2011.011018
Evaluation of 25-hydroxy vitamin D assay on the immunodiagnostic systems iSYS analyser
Zee N Cluse (2012)
10.1042/cs0540329
A radioimmunoassay for 1,25-dihydroxycholecalciferol.
R. Bouillon (1980)
10.1255/ejms.1024
Development of a Method for the Quantification of 1α,25(OH)2–Vitamin D3 in Serum by Liquid Chromatography Tandem Mass Spectrometry without Derivatization
B. Casetta (2010)
10.1093/clinchem/25.4.584
Assay of 1,25-dihydroxy vitamin D3 by isotope dilution--mass fragmentography.
I. Björkhem (1979)
10.1016/0009-8981(74)90241-1
A competitive protein-binding assay for 25-hydroxycholecalciferol and 25-hydroxyergocalciferol in serum.
M. Preece (1974)
Radioreceptor assay for 1 alpha,25-dihydroxyvitamin D3.
P. Brumbaugh (1974)
10.1093/clinchem/41.9.1313
1,25-Dihydroxyvitamin D3-26,23-lactone interferes in determination of 1,25-dihydroxyvitamin D by RIA after immunoextraction.
B. Hollis (1995)
10.1042/cs0550213
Intestinal cholecalciferol absorption in the elderly and in younger adults.
J. Barragry (1978)
10.1016/0009-8981(82)90239-X
Measurement of circulating vitamin D in man.
T. Clemens (1982)
10.1210/jc.86.2.888
Extrarenal Expression of 25-Hydroxyvitamin D 3-1 a-Hydroxylase *
Daniel Zehnder (2001)
10.1016/J.YPAT.2012.07.043
Accuracy of 6 Routine 25-Hydroxyvitamin D Assays: Influence of Vitamin D Binding Protein Concentration
M. Bissell (2013)
10.1021/ac202047n
Development and certification of a standard reference material for vitamin D metabolites in human serum.
K. Phinney (2012)
Routine isotopedilution liquid chromatography-tandem mass spectrometry assay for simultaneous measurement of the 25-hydroxy metabolites of vitamins D 2 and D 3
Z Maunsell (2005)
10.1016/0003-2697(77)90648-0
Determination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in human plasma using high-pressure liquid chromatography.
J. Eisman (1977)
10.1210/JCEM.86.2.7220
Extrarenal Expression of 25-Hydroxyvitamin D3-1α-Hydroxylase1
D. Zehnder (2001)
10.1373/clinchem.2010.157115
Increasing liquid chromatography-tandem mass spectrometry throughput by mass tagging: a sample-multiplexed high-throughput assay for 25-hydroxyvitamin D2 and D3.
Brian C. Netzel (2011)
10.1016/0003-9861(80)90404-X
Plasma concentrations of vitamin D3 and its metabolites in the rat as influenced by vitamin D3 or 25-hydroxyvitamin D3 intakes.
R. Shephard (1980)
10.1002/rcm.4988
Sensitive measurement of serum 1α,25-dihydroxyvitamin D by liquid chromatography/tandem mass spectrometry after removing interference with immunoaffinity extraction.
C. Yuan (2011)
10.1093/clinchem/27.3.458
A modified radioimmunoassay for 1,25-dihydroxycholecalciferol.
T. Gray (1981)
10.1373/CLINCHEM.2005.048355
Underestimation of serum 25-hydroxyvitamin D by the Nichols Advantage Assay in patients receiving vitamin D replacement therapy.
P. Leventis (2005)
10.1016/j.jchromb.2011.12.021
Development and optimization of simplified LC-MS/MS quantification of 25-hydroxyvitamin D using protein precipitation combined with on-line solid phase extraction (SPE).
D. Thibeault (2012)
10.1093/AJCN/88.2.582S
Pharmacokinetics of vitamin D toxicity.
G. Jones (2008)
10.1373/clinchem.2010.152553
Candidate reference measurement procedures for serum 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 by using isotope-dilution liquid chromatography-tandem mass spectrometry.
H. Stepman (2011)
Sensitive analysis of 1alpha,25-dihydroxyvitamin D3 in biological fluids by liquid chromatography-tandem mass spectrometry.
A. Kissmeyer (2001)
10.1021/AC048249C
Determination of 25-hydroxyvitamin D in human plasma using high-performance liquid chromatography--tandem mass spectrometry.
N. Tsugawa (2005)
10.1093/clinchem/39.3.529
Determination of vitamin D status by radioimmunoassay with an 125I-labeled tracer.
B. Hollis (1993)
10.1210/jc.2012-2790
Effect of a 300 000-IU loading dose of ergocalciferol (Vitamin D2) on circulating 1,25(OH)2-vitamin D and fibroblast growth factor-23 (FGF-23) in vitamin D insufficiency.
C. Turner (2013)
10.1093/clinchem/31.11.1815
Improved radioimmunoassay for vitamin D and its use in assessing vitamin D status.
B. W. Hollis (1985)
I-based RIA methods for the determination of circulating 25-hydroxyvitamin D
Quantification of 1a,25-dihydroxy vitamin D by immunoextraction and liquid chromatography-tandem mass spectrometry
Fg Strathmann (2011)
10.1210/JC.2006-0710
C-3 epimers can account for a significant proportion of total circulating 25-hydroxyvitamin D in infants, complicating accurate measurement and interpretation of vitamin D status.
R. Singh (2006)
10.1016/0002-9343(74)90768-2
Circulating 25-hydroxyvitamin D in man.
J. Haddad (1974)
10.1021/ac902869y
Ultrasensitive quantification of serum vitamin D metabolites using selective solid-phase extraction coupled to microflow liquid chromatography and isotope-dilution mass spectrometry.
X. Duan (2010)
10.1210/edrv-16-2-200
Structure-function relationships in the vitamin D endocrine system.
R. Bouillon (1995)
10.1373/clinchem.2010.154997
Clinical applications for vitamin D assays: what is known and what is wished for.
M. Kleerekoper (2011)
10.1186/1475-2891-10-46
Misleading measures in Vitamin D analysis: A novel LC-MS/MS assay to account for epimers and isobars
Iltaf Shah (2011)
Competitive protein-binding radioassay for 25-hydroxycholecalciferol.
J. Haddad (1971)
10.1111/j.1365-2265.1983.tb02977.x
RADIOIMMUNOASSAY OF 1,25‐DIHYDROXY VITAMIN D2: STUDIES ON THE METABOLISM OF VITAMIN D2 IN MAN
L. Fraher (1983)
10.1093/clinchem/23.9.1700
High-performance liquid chromatographic assay for 25-hydroxyvitamin D3 in serum.
T. Gilbertson (1977)
10.1016/j.cca.2011.11.014
Human anti-animal interference in DiaSorin Liaison total 25(OH)-vitamin D assay: towards the end of a strange story?
Etienne Cavalier (2012)
10.1210/jcem-33-6-992
COMPETITIVE PROTEIN-BINDING RADIOASSAY FOR 25-HYDROXYCHOLECALCIFEROL1
J. Haddad (1971)
10.1210/jcem-63-3-656
Serum vitamin D2 and vitamin D3 metabolite concentrations and absorption of vitamin D2 in elderly subjects.
T. Clemens (1986)
10.1373/CLINCHEM.2004.031831
Candidate reference method for the quantification of circulating 25-hydroxyvitamin D3 by liquid chromatography-tandem mass spectrometry.
M. Vogeser (2004)
10.1258/000456303322326470
Issues of methodology, standardization and metabolite recognition for 25-hydroxyvitamin D when comparing the DiaSorin radioimmunoassay and the Nichols Advantage automated chemiluminescence protein-binding assay in hip fracture cases
P. Glendenning (2003)
10.1373/CLINCHEM.2004.040683
How accurate are assays for 25-hydroxyvitamin D? Data from the international vitamin D external quality assessment scheme.
G. Carter (2004)
10.1007/s00216-008-2095-8
Metabolic profiling of major vitamin D metabolites using Diels–Alder derivatization and ultra-performance liquid chromatography–tandem mass spectrometry
P. Aronov (2008)
Assay of Vitamins D 2 and D 3 , and 25-Hydroxyvitamins D 2 and D 3 in Human Plasma by High-Performance Liquid Chromatography
Jones
Uskokovic MR (1980) A radioimmunoassay for 1,25-dihydroxycholecalciferol
R Bouillon (1980)
10.1016/j.jsbmb.2010.03.033
Proficiency testing of 25-Hydroxyvitamin D (25-OHD) assays
G. D. Carter (2010)
10.1002/RCM.908
Ion suppression in the determination of clenbuterol in urine by solid-phase extraction atmospheric pressure chemical ionisation ion-trap mass spectrometry.
M. V. van Hout (2003)
State-oftheArt oftheArt oftheArt theArt theArt Vitamin D Assays : A Comparison of Automated Immunoassays with Liquid Chromatography – Tandem Mass Spectrometry Methods
Christopher-John L Farrell (2012)
10.1016/J.CLINBIOCHEM.2004.06.006
Analytical and clinical validation of the 25 OH vitamin D assay for the LIAISON automated analyzer.
D. Ersfeld (2004)
10.1210/jcem-46-5-756
Metabolism and excretion of 3H-1,25-(OH)2-vitamin D3 in healthy adults.
R. Gray (1978)
10.1258/000456306775141650
Current assays overestimate 25-hydroxyvitamin D3 and underestimate 25-hydroxyvitamin D2 compared with HPLC: need for assay-specific decision limits and metabolite-specific assays
P. Glendenning (2006)
Improved methodology for the analysis of plasma vitamin D metabolites.
R. Horst (1990)
10.1093/clinchem/30.7.1193
Specific estimation of 24,25-dihydroxyvitamin D in plasma by gas chromatography-mass spectrometry.
R. D. Coldwell (1984)
10.1002/bms.1200221102
On-line post-column Diels-Alder derivatization for the determination of vitamin D3 and its metabolites by liquid chromatography/thermospray mass spectrometry.
R. Vreeken (1993)
10.1373/clinchem.2011.180562
25-hydroxyvitamin D: a difficult analyte.
G. Carter (2012)
10.1016/j.jocd.2009.06.001
25-hydroxyvitamin D measurement, 2009: a review for clinicians.
N. Binkley (2009)
10.1258/acb.2008.008225
Standardization of vitamin D assays: art or science?
W. Fraser (2009)
10.1126/science.183.4129.1089
Radioreceptor Assay for 1α,25-Dihydroxyvitamin D3
P. Brumbaugh (1974)
10.1515/CCLM.2009.342
Development and validation of a liquid chromatography-tandem mass spectrometry assay for serum 25-hydroxyvitamin D2/D3 using a turbulent flow online extraction technology
Dustin R. Bunch (2009)
10.1042/cs0620427
The effect of renal function on changes in circulating concentrations of 1,25-dihydroxycholecalciferol after an oral dose.
S. Papapoulos (1982)
10.1258/acb.2008.008135
Use of a common standard improves the performance of liquid chromatography-tandem mass spectrometry methods for serum 25-hydroxyvitamin-D
G. Carter (2009)
10.1210/JC.2007-1279
Serum 25-hydroxyvitamin D measurement in a large population survey with statistical harmonization of assay variation to an international standard.
E. Hyppönen (2007)
Comparison of commercially available 125
Bw Hollis (2000)
10.1210/jcem-58-1-91
A microassay for 1,25-dihydroxyvitamin D not requiring high performance liquid chromatography: application to clinical studies.
T. Reinhardt (1984)
10.1210/jcem-33-3-554
Competitive binding assay for vitamin D and 25-OH vitamin D.
R. Belsey (1971)
10.1210/jc.2011-0584
The C-3 epimer of 25-hydroxyvitamin D(3) is present in adult serum.
G. Lensmeyer (2012)
10.1373/CLINCHEM.2005.064956
HPLC method for 25-hydroxyvitamin D measurement: comparison with contemporary assays.
G. Lensmeyer (2006)
10.1177/000456329703400606
Measurement of Plasma 1,25 Dihydroxyvitamin D Using a Novel Immunoextraction Technique and Immunoassay with Iodine Labelled Vitamin D Tracer
W. Fraser (1997)
10.1373/CLINCHEM.2005.052936
Routine isotope-dilution liquid chromatography-tandem mass spectrometry assay for simultaneous measurement of the 25-hydroxy metabolites of vitamins D2 and D3.
Z. Maunsell (2005)
10.1111/j.1365-2362.1972.tb00644.x
Measurement of Plasma 25‐Hydroxycholecalciferol in Man
F. Bayard (1972)
10.1093/clinchem/24.2.287
Assay of vitamins D2 and D3, and 25-hydroxyvitamins D2 and D3 in human plasma by high-performance liquid chromatography.
G. Jones (1978)
10.1007/BF02555135
Low circulating vitamin D in obesity
Y. Liel (2007)
10.1093/clinchem/42.4.586
Quantification of circulating 1,25-dihydroxyvitamin D by radioimmunoassay with 125I-labeled tracer.
B. Hollis (1996)
10.1258/acb.2009.008206
A simple automated solid-phase extraction procedure for measurement of 25-hydroxyvitamin D3 and D2 by liquid chromatography-tandem mass spectrometry
S. Knox (2009)
10.3945/jn.110.121483
NHANES monitoring of serum 25-hydroxyvitamin D: a roundtable summary.
E. Yetley (2010)
10.1359/jbmr.080607
Vitamin D Metabolites and Calcium Absorption in Severe Vitamin D Deficiency
A. Need (2008)
10.1530/eje.0.1300141
Acute effects of intravenous 1 alpha-hydroxycholecalciferol on parathyroid hormone, osteocalcin and calcitriol in man.
S. Gallacher (1994)
Importance of the isolation of 25-hydroxyvitamin D before assay.
L. Dorantes (1978)
Characterization of vitamin D 3 metabolites using continuous-flow fast atom bombardment tandem mass spectrometry and high-performance liquid chromatography
B Yeung (1993)
10.1373/CLINCHEM.2006.077560
Evaluation of a 1,25-dihydroxyvitamin D enzyme immunoassay.
I. Seiden-Long (2007)
10.1016/S0021-9673(01)00985-2
Sensitive analysis of 1α,25-dihydroxyvitamin D3 in biological fluids by liquid chromatography–tandem mass spectrometry
A. Kissmeyer (2001)
10.1042/cs0460231
Competitive protein-binding assay for 25-hydroxycholecalciferol.
S. Edelstein (1974)



This paper is referenced by
10.1177/201010581302200311
Vitamin D Measurements — Facts and Fancies
Tar Choon Aw (2013)
10.1016/S2213-8587(13)70083-4
Subclinical and asymptomatic parathyroid disease: implications of emerging data.
D. Macfarlane (2013)
10.1016/B978-0-12-800871-3.00009-2
Vitamin D metabolite quantitation by LC-MS/MS
Hemamalini Ketha (2017)
10.1038/s41430-019-0448-3
Vitamin D supplementation has no effects on progression of motor dysfunction in amyotrophic lateral sclerosis (ALS)
F. Trojsi (2019)
Wpływ witaminy D3 na kruchość kulinarnego mięsa wołowego
U. Rafalska (2014)
10.1080/02640414.2015.1033642
The effect of 14 weeks of vitamin D3 supplementation on antimicrobial peptides and proteins in athletes
Cheng-Shiun He (2016)
Vitamin D and Bone Health: A Practical Clinical Guideline for Patient Management
V I T (2013)
10.14264/uql.2018.384
Development of an assay for vitamin D in biological samples
Abu Baker Kassim (2018)
10.1586/eci.13.19
Vitamin D and systemic lupus erythematosus: an update
C. C. Mok (2013)
10.7939/R31Z4242X
The prevalence and determinants of adequate vitamin D intake and supplementation among Canadian children
Dona Ll. Munasinghe (2016)
10.1007/s11657-014-0188-x
Milk fortified with vitamin D could reduce the prevalence of vitamin D deficiency among Japanese female college students
Y. Suzuki (2014)
10.1097/MJT.0000000000000538
Magnesium Supplementation in Vitamin D Deficiency
P. Reddy (2019)
10.1542/peds.2014-1860
Vitamin D in Fetal Development: Findings From a Birth Cohort Study
P. Hart (2015)
10.1007/978-1-4614-8503-2_53-1
Intensive Care and Vitamin D Status
Dima A. Youssef (2014)
Vitamin D Testing in Clinical Settings: Methodologies, Accuracy and Standardization
Fakhri B Saida (2018)
10.4103/2008-7802.195212
Effects of Iron on Vitamin D Metabolism: A Systematic Review
Fatemeh Azizi-soleiman (2016)
10.1080/09674845.2016.1188478
Automated measurement of 25-OH Vitamin D on the LUMIPULSE® G1200: analytical verification and method comparison
Marina Parra (2016)
10.1515/cclm-2019-0834
Evaluation of the 25-hydroxy vitamin D assay on a fully automated liquid chromatography mass spectrometry system, the Thermo Scientific Cascadion SM Clinical Analyzer with the Cascadion 25-hydroxy vitamin D assay in a routine clinical laboratory
Sally C Benton (2019)
10.1371/journal.pone.0091363
Impact of Vitamin D Supplementation on Arterial Vasomotion, Stiffness and Endothelial Biomarkers in Chronic Kidney Disease Patients
N. Chitalia (2014)
10.1186/s12958-020-00644-6
Correlation of low serum vitamin-D with uterine leiomyoma: a systematic review and meta-analysis
Ramin Mohammadi (2020)
10.1016/j.jand.2017.10.009
Prevalence and Predictors of Low Serum 25-Hydroxyvitamin D among Female African-American Breast Cancer Survivors.
P. Sheean (2018)
10.1530/EJE-13-0435
Management of endocrine disease: value and limitations of assessing vitamin D nutritional status and advised levels of vitamin D supplementation.
E. Romagnoli (2013)
10.7326/M14-1659
Screening for Vitamin D Deficiency: A Systematic Review for the U.S. Preventive Services Task Force
E. LeBlanc (2015)
10.3109/00365513.2013.869701
Serum free and bio-available 25-hydroxyvitamin D correlate better with bone density than serum total 25-hydroxyvitamin D
M. S. Johnsen (2014)
10.3390/nu8110717
Older Swedish Adults with High Self-Perceived Health Show Optimal 25-Hydroxyvitamin D Levels Whereas Vitamin D Status Is Low in Patients with High Disease Burden
M. Carlsson (2016)
10.1016/j.cca.2015.01.029
Prevalence of 25-hydroxyvitamin D₂ in Western New York: a 3-year study.
Yan Victoria Zhang (2015)
Vitamin D and exercise performance : influence of simulated sunlight and oral supplementation
Alexander T. Carswell (2019)
A importância clínica da vitamina D
Tânia Marisa Macedo Pinheiro (2015)
10.1177/2333721417697843
Social Disadvantage Is Associated With Lower Vitamin D Levels in Older People and There Is No Surrogate for Its Measurement
A. Heald (2017)
10.3390/nu11020243
Vitamin D in the Prevention and Treatment of Osteoarthritis: From Clinical Interventions to Cellular Evidence
Clara Yongjoo Park (2019)
10.16966/2572-9578.132
A High Throughput Universal Vitamin D Assay for Automated Chemistry Analyzers
Saida Fb (2019)
10.1097/MCO.0b013e328364ca96
Critical evaluation of assays for vitamin D status
F. G. Lorencio (2013)
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