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Vitamin D and metabolites measurement by tandem mass spectrometry

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Abstract

The prevalence of vitamin D deficiency in the general population has become a major public health problem. Vitamin D deficiency might have significant consequences not only to bone health but possibly to autoimmune-, infectious and cardiovascular disease. This has resulted in increased clinical testing for 25-hydroxyvitamin D (25(OH)D) in serum, as circulating 25(OH)D is regarded as the best indicator of adequate exposure to sunlight and dietary intake of vitamin D. There are reportedly over 50 vitamin D metabolites of which 25(OH)D and 1,25(OH)2D are well known to provide clinical information. More recently, there is increasing interest in measuring the C3-epimer of 25(OH)D, which has shown to contribute significantly to the 25(OH)D concentration, particularly in infant populations, and in 24,25(OH)2D, a major catabolite of 25(OH)D metabolism. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an analytical tool that allows the specific determination of all relevant vitamin D metabolites, with the potential of performing multiple analyte analysis in a single experimental setting, creating a vitamin D profile. This article reviews recent advances in the quantification of vitamin D metabolites using LC-MS/MS.

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Abbreviations

1,25(OH)2D:

1,25-dihydroxyvitamin D

24R,25(OH)2D3 :

24R,25-dihydroxyvitamin D3

25(OH)D:

25-hydroxyvitamin D

3-epi-25(OH)D:

3-epi-25-hydroxyvitamin D

APCI:

Atmospheric pressure chemical ionisation

APPI:

Atmospheric pressure photo ionisation

CV:

Coefficient of variation

DBS:

Dried blood spots

DEQAS:

Vitamin D external quality assessment scheme

ESI:

Electrospray ionisation

GC-MS:

Gas chromatography mass spectrometry

ID:

Isotope dilution

LC-MS/MS:

Liquid chromatography tandem mass spectrometry

LLE:

Liquid liquid extraction

LLOQ:

Lower limit of quantification

MRM:

Multi reaction monitoring

NIST:

National Institute of Standards and Technology

PFP:

Pentafluorophenyl

PTH:

Parathyroid hormone

PTAD:

4-phenly-1,2,4-triazoline-3,5-dione

RIA:

Radio immunoassay

RRA:

Radio receptor assay

SPE:

Solid phase extraction

SRM:

Standard reference material

VDBP:

Vitamin D binding protein

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  1. Department of Clinical Chemistry, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands

    Johannes M. W. van den Ouweland

  2. Institute of Laboratory Medicine, Hospital of the University of Munich, Marchioninistr. 15, 81377, Munich, Germany

    Michael Vogeser & Silvia Bächer

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  1. Johannes M. W. van den Ouweland
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Correspondence to Michael Vogeser.

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van den Ouweland, J.M.W., Vogeser, M. & Bächer, S. Vitamin D and metabolites measurement by tandem mass spectrometry. Rev Endocr Metab Disord 14, 159–184 (2013). https://doi.org/10.1007/s11154-013-9241-0

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