Top

Reviews in Endocrine and Metabolic Disorders

Published in:

01-06-2013

Vitamin D and metabolites measurement by tandem mass spectrometry

Authors: Johannes M. W. van den Ouweland, Michael Vogeser, Silvia Bächer

Published in: Reviews in Endocrine and Metabolic Disorders | Issue 2/2013

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.

Hintzpeter B, Mensink GB, Thierfelder W, Muller MJ, Scheidt-Nave C. Vitamin D status and health correlates among German adults. Eur J Clin Nutr. 2008;62(9):1079–89. doi:10.1038/sj.ejcn.1602825.PubMedCrossRef

Arabi A, El Rassi R, El-Hajj Fuleihan G. Hypovitaminosis D in developing countries[mdash]prevalence, risk factors and outcomes. Nat Rev Endocrinol. 2010;6(10):550–61. doi:10.1038/nrendo.2010.146.PubMedCrossRef

Sattar N, Welsh P, Panarelli M, Forouhi NG. Increasing requests for vitamin D measurement: costly, confusing, and without credibility. Lancet. 2012;379(9811):95–6.PubMedCrossRef

Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81. doi:10.1056/NEJMra070553.

Jones G. Metabolism and biomarkers of Vitamin D. Scand J Clin Lab Invest. 2012;72(S243):7–13. doi:10.3109/00365513.2012.681892.

Zerwekh JE. Blood biomarkers of vitamin D status. Am J Clin Nutr. 2008;87(4):1087S–91S.PubMed

Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D, et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010;376(9736):180–8.PubMedCrossRef

Binkley N, Krueger D, Cowgill CS, Plum L, Lake E, Hansen KE, et al. Assay variation confounds the diagnosis of hypovitaminosis D: a call for standardization. J Clin Endocrinol Metab. 2004;89(7):3152–7. doi:10.1210/jc.2003-031979.

Higashi T, Awada D, Shimada K. Simultaneous determination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in human plasma by liquid chromatography-tandem mass spectrometry employing derivatization with a Cookson-type reagent. Biol Pharm Bull. 2001;24(7):738–43.

10.

Vogeser M, Kyriatsoulis A, Huber E, Kobold U. Candidate reference method for the quantification of circulating 25-hydroxyvitamin D3 by liquid chromatography-tandem mass spectrometry. Clin Chem. 2004;50(8):1415–7. doi:10.1373/clinchem.2004.031831.PubMedCrossRef

11.

Stepman HC, Vanderroost A, Van Uytfanghe K, Thienpont LM. Candidate reference measurement procedures for serum 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 by using isotope-dilution liquid chromatography-tandem mass spectrometry. Clin Chem. 2011;57(3):441–8. doi:10.1373/clinchem.2010.152553.PubMedCrossRef

12.

Tai SS, Bedner M, Phinney KW. 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. Anal Chem. 2010;82(5):1942–8. doi:10.1021/ac9026862.

13.

Thienpont LM, Stepman HCM, Vesper HW. Standardization of measurements of 25-Hydroxyvitamin D3 and D2. Scand J Clin Lab Invest. 2012;72(S243):41–9. doi:10.3109/00365513.2012.681950.

14.

Adamec J, Jannasch A, Huang J, Hohman E, Fleet JC, Peacock M, et al. Development and optimization of an LC-MS/MS-based method for simultaneous quantification of vitamin D2, vitamin D3, 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3. J Sep Sci. 2011;34(1):11–20. doi:10.1002/jssc.201000410.

15.

Cai S-S, Syage JA. Comparison of atmospheric pressure photoionization, atmospheric pressure chemical ionization, and electrospray ionization mass spectrometry for analysis of lipids. Anal Chem. 2006;78(4):1191–9. doi:10.1021/ac0515834.PubMedCrossRef

16.

Blum M, Dolnikowski G, Seyoum E, Harris S, Booth S, Peterson J, et al. Vitamin D<sub>3</sub>in fat tissue. Endocrine. 2008;33(1):90–4. doi:10.1007/s12020-008-9051-4.PubMedCrossRef

17.

Mawer EB, Backhouse J, Holman CA, Lumb GA, Stanbury SW. The distribution and storage of vitamin D and its metabolites in human tissues. Clin Sci. 1972;43(3):413–31.PubMed

18.

Vieth R. The pharmacology of vitamin D. In: Feldman D, Pike JW, Adams JS, editors. Vitamin D. 3rd ed., Vol. Volume I. Academic Press, London, UK; 2011. pp. 1041–1066.

19.

Robinson PD, Högler W, Craig ME, Verge CF, Walker JL, Piper AC, et al. The re-emerging burden of rickets: a decade of experience from Sydney. Arch Dis Child. 2006;91(7):564–8. doi:10.1136/adc.2004.069575.PubMedCrossRef

20.

Bischoff-Ferrari HA, Willett WC, Orav EJ, Lips P, Meunier PJ, Lyons RA, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012;367(1):40–9. doi:10.1056/NEJMoa1109617.PubMedCrossRef

21.

Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53–8. doi:10.1210/jc.2010-2704.PubMedCrossRef

22.

Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30. doi:10.1210/jc.2011-0385.

23.

Haddad JG, Chyu KJ. Competitive protein-binding radioassay for 25-hydroxycholecalciferol. J Clin Endocrinol Metab. 1971;33(6):992–5. doi:10.1210/jcem-33-6-992.PubMedCrossRef

24.

Hollis BW. Assessment and interpretation of circulating 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in the clinical environment. Rheum Dis Clin N Am. 2012;38(1):29–44. doi:10.1016/j.rdc.2012.03.005.CrossRef

25.

van den Ouweland JM, Beijers AM, Demacker PN, van Daal H. Measurement of 25-OH-vitamin D in human serum using liquid chromatography tandem-mass spectrometry with comparison to radioimmunoassay and automated immunoassay. J Chromatogr B Anal Technol Biomed Life Sci. 2010;878(15–16):1163–8. doi:10.1016/j.jchromb.2010.03.035.

26.

Roth HJ, Schmidt-Gayk H, Weber H, Niederau C. Accuracy and clinical implications of seven 25-hydroxyvitamin D methods compared with liquid chromatography-tandem mass spectrometry as a reference. Ann Clin Biochem. 2008;45(2):153–9. doi:10.1258/acb.2007.007091.PubMedCrossRef

27.

Farrell C-JL, Martin S, McWhinney B, Straub I, Williams P, Herrmann M. State-of-the-Art vitamin D assays: a comparison of automated immunoassays with liquid chromatography-tandem mass spectrometry methods. Clin Chem. 2012;58(3):531–42. doi:10.1373/clinchem.2011.172155.PubMedCrossRef

28.

Eisman JA, Shepard RM, DeLuca HF. Determination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in human plasma using high-pressure liquid chromatography. Anal Biochem. 1977;80(1):298–305. doi:10.1016/0003-2697(77)90648-0.PubMedCrossRef

29.

De Leenheer AP, Cruyl AA. Vitamin D3 in plasma: quantitation by mass fragmentography. Anal Biochem. 1978;91(1):293–303. doi:10.1016/0003-2697(78)90843-6.PubMedCrossRef

30.

Watson D, Setchell KDR, Ross R. Analysis of vitamin D and its metabolites using thermospray liquid chromatography/mass spectrometry. Biomed Chromatogr. 1991;5(4):153–60. doi:10.1002/bmc.1130050404.PubMedCrossRef

31.

El-Khoury JM, Reineks EZ, Wang S. Progress of liquid chromatography-mass spectrometry in measurement of vitamin D metabolites and analogues. [Review]. Clin Biochem. 2011;44(1):66–76. doi:10.1016/j.clinbiochem.2010.05.007.PubMedCrossRef

32.

Higashi T, Shimada K, Toyo’oka T. Advances in determination of vitamin D related compounds in biological samples using liquid chromatography-mass spectrometry: a review. [Review]. J Chromatogr B Anal Technol Biomed Life Sci. 2010;878(20):1654–61. doi:10.1016/j.jchromb.2009.11.026.CrossRef

33.

Vogeser M. Quantification of circulating 25-hydroxyvitamin D by liquid chromatography-tandem mass spectrometry. [Review]. J Steroid Biochem Mol Biol. 2010;121(3–5):565–73. doi:10.1016/j.jsbmb.2010.02.025.PubMedCrossRef

34.

Vogeser M, Seger C. Pitfalls associated with the use of liquid chromatography-tandem mass spectrometry in the clinical laboratory. [Review]. Clin Chem. 2010;56(8):1234–44. doi:10.1373/clinchem.2009.138602.PubMedCrossRef

35.

Bogusz MJ, Al Enazi E, Tahtamoni M, Jawaad JA, Al Tufail M. Determination of serum vitamins 25-OH-D2 and 25-OH-D3 with liquid chromatography-tandem mass spectrometry using atmospheric pressure chemical ionization or electrospray source and core-shell or sub-2 mum particle columns: a comparative study. Clin Biochem. 2011;44(16):1329–37. doi:10.1016/j.clinbiochem.2011.08.1134.PubMedCrossRef

36.

Herrmann M, Harwood T, Gaston-Parry O, Kouzios D, Wong T, Lih A, et al. A new quantitative LC tandem mass spectrometry assay for serum 25-hydroxy vitamin D. Steroids. 2010;75(13–14):1106–12. doi:10.1016/j.steroids.2010.07.006.PubMedCrossRef

37.

Musteata ML, Musteata FM. Overview of extraction methods for analysis of vitamin D and its metabolites in biological samples. Bioanalysis. 2011;3(17):1987–2002. doi:10.4155/bio.11.195.

38.

Couchman L, Benton CM, Moniz CF. Variability in the analysis of 25-hydroxyvitamin D by liquid chromatography-tandem mass spectrometry: the devil is in the detail. Clin Chim Acta. 2012;413(15–16):1239–43. doi:10.1016/j.cca.2012.04.003.PubMedCrossRef

39.

Elder PA, Lewis JG, King RI, Florkowski CM. An anomalous result from gel tubes for vitamin D. Clin Chim Acta. 2009;410(1–2):95. doi:10.1016/j.cca.2009.09.037.PubMedCrossRef

40.

Higashi T, Shibayama Y, Fuji M, Shimada K. Liquid chromatography-tandem mass spectrometric method for the determination of salivary 25-hydroxyvitamin D3: a noninvasive tool for the assessment of vitamin D status. Anal Bioanal Chem. 2008;391(1):229–38. doi:10.1007/s00216-007-1780-3.

41.

Higashi T, Suzuki M, Hanai J, Inagaki S, Min JZ, Shimada K, et al. A specific LC/ESI-MS/MS method for determination of 25-hydroxyvitamin D3 in neonatal dried blood spots containing a potential interfering metabolite, 3-epi-25-hydroxyvitamin D3. J Sep Sci. 2011;34(7):725–32. doi:10.1002/jssc.201000911.

42.

Shah I, James R, Barker J, Petroczi A, Naughton DP. Misleading measures in Vitamin D analysis: a novel LC-MS/MS assay to account for epimers and isobars. Nutr J. 2011;10:46. doi:10.1186/1475-2891-10-46.PubMedCrossRef

43.

Saenger AK, Laha TJ, Bremner DE, Sadrzadeh SM. Quantification of serum 25-hydroxyvitamin D(2) and D(3) using HPLC-tandem mass spectrometry and examination of reference intervals for diagnosis of vitamin D deficiency. Am J Clin Pathol. 2006;125(6):914–20. doi:10.1309/J32U-F7GT-QPWN-25AP.

44.

Bunch DR, Miller AY, Wang S. Development and validation of a liquid chromatography-tandem mass spectrometry assay for serum 25-hydroxyvitamin D2/D3 using a turbulent flow online extraction technology. Clin Chem Lab Med. 2009;47(12):1565–72.PubMedCrossRef

45.

Thibeault D, Caron N, Djiana R, Kremer R, Blank D. Development and optimization of simplified LC-MS/MS quantification of 25-hydroxyvitamin D using protein precipitation combined with on-line solid phase extraction (SPE). J Chromatogr B. 2012;883–884:120–7. doi:10.1016/j.jchromb.2011.12.021.CrossRef

46.

Kushnir MM, Ray JA, Rockwood AL, Roberts WL, La’ulu SL, Whittington JE, et al. Rapid analysis of 25-hydroxyvitamin D2 and D3 by liquid chromatography-tandem mass spectrometry and association of vitamin D and parathyroid hormone concentrations in healthy adults. Am J Clin Pathol. 2010;134(1):148–56. doi:10.1309/ajcppia7dfbt4gks.PubMedCrossRef

47.

Yuan C, Kosewick J, He X, Kozak M, Wang S. Sensitive measurement of serum 1α,25-dihydroxyvitamin D by liquid chromatography/tandem mass spectrometry after removing interference with immunoaffinity extraction. Rapid Commun Mass Spectrom. 2011;25(9):1241–9. doi:10.1002/rcm.4988.PubMedCrossRef

48.

Chen H, McCoy LF, Schleicher RL, Pfeiffer CM. 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. Clin Chim Acta. 2008;391(1–2):6–12. doi:10.1016/j.cca.2008.01.017.

49.

Duan X, Weinstock-Guttman B, Wang H, Bang E, Li J, Ramanathan M, et al. Ultrasensitive quantification of serum vitamin D metabolites using selective solid-phase extraction coupled to microflow liquid chromatography and isotope-dilution mass spectrometry. Anal Chem. 2010;82(6):2488–97. doi:10.1021/ac902869y.

50.

Maunsell Z, Wright DJ, Rainbow SJ. Routine isotope-dilution liquid chromatography-tandem mass spectrometry assay for simultaneous measurement of the 25-hydroxy metabolites of vitamins D2 and D3. Clin Chem. 2005;51(9):1683–90. doi:10.1373/clinchem.2005.052936.

51.

Knox S, Harris J, Calton L, Wallace AM. A simple automated solid-phase extraction procedure for measurement of 25-hydroxyvitamin D3 and D2 by liquid chromatography-tandem mass spectrometry. Ann Clin Biochem. 2009;46(Pt 3):226–30. doi:10.1258/acb.2009.008206.PubMedCrossRef

52.

Netzel BC, Cradic KW, Bro ET, Girtman AB, Cyr RC, Singh RJ, et al. Increasing liquid chromatography-tandem mass spectrometry throughput by mass tagging: a sample-multiplexed high-throughput assay for 25-hydroxyvitamin D2 and D3. Clin Chem. 2011;57(3):431–40. doi:10.1373/clinchem.2010.157115.PubMedCrossRef

53.

Højskov CS, Heickendorff L, Møller HJ. High-throughput liquid-liquid extraction and LCMSMS assay for determination of circulating 25(OH) vitamin D3 and D2 in the routine clinical laboratory. Clin Chim Acta. 2010;411(1–2):114–6. doi:10.1016/j.cca.2009.10.010.PubMedCrossRef

54.

Jones G, Prosser DE. The activating enzymes of vitamin D metabolism (25- and 1alpha-Hydroxylases). In: Feldman D, Pike JW, Adams JS, editors. Vitamin D, Vol. Volume I. Academic Press, London, UK; 2011. pp. 23–42.

55.

Strathmann FG, Laha TJ, Hoofnagle AN. Quantification of 1alpha,25-dihydroxy vitamin D by immunoextraction and liquid chromatography-tandem mass spectrometry. Clin Chem. 2011;57(9):1279–85. doi:10.1373/clinchem.2010.161174.

56.

Brumbaugh PF, Haussler DH, Bursac KM, Haussler MR. Filter assay for 1alpha, 25-dihydroxyvitamin D3. Utilization of the hormone’s target tissue chromatin receptor. Biochemistry. 1974;13(20):4091–7.

57.

Hollis BW. 1,25-Dihydroxyvitamin D3-26,23-lactone interferes in determination of 1,25-dihydroxyvitamin D by RIA after immunoextraction. Clin Chem. 1995;41(9):1313–4.PubMed

58.

Kissmeyer A-M, Sonne K. Sensitive analysis of 1α,25-dihydroxyvitamin D3 in biological fluids by liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2001;935(1–2):93–103. doi:10.1016/s0021-9673(01)00985-2.PubMed

59.

Casetta B, Jans I, Billen J, Vanderschueren D, Bouillon R. Development of a method for the quantification of 1alpha,25(OH)2-vitamin D3 in serum by liquid chromatography tandem mass spectrometry without derivatization. Eur J Mass Spectrom (Chichester, Eng). 2010;16(1):81–9. doi:10.1255/ejms.1024.

60.

Aronov PA, Hall LM, Dettmer K, Stephensen CB, Hammock BD. Metabolic profiling of major vitamin D metabolites using Diels-Alder derivatization and ultra-performance liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2008;391(5):1917–30. doi:10.1007/s00216-008-2095-8.

61.

Wang Z, Senn T, Kalhorn T, Zheng XE, Zheng S, Davis CL, et al. Simultaneous measurement of plasma vitamin D(3) metabolites, including 4beta,25-dihydroxyvitamin D(3), using liquid chromatography-tandem mass spectrometry. Anal Biochem. 2011;418(1):126–33. doi:10.1016/j.ab.2011.06.043.

62.

Ding S, Schoenmakers I, Jones K, Koulman A, Prentice A, Volmer DA. Quantitative determination of vitamin D metabolites in plasma using UHPLC-MS/MS. Anal Bioanal Chem. 2010;398(2):779–89. doi:10.1007/s00216-010-3993-0.

63.

Tsikas D. Quantitative analysis of biomarkers, drugs and toxins in biological samples by immunoaffinity chromatography coupled to mass spectrometry or tandem mass spectrometry: A focused review of recent applications. J Chromatogr B. 2010;878(2):133–48. doi:10.1016/j.jchromb.2009.11.008.CrossRef

64.

Kamao M, Tatematsu S, Hatakeyama S, Sakaki T, Sawada N, Inouye K, et al. C-3 epimerization of vitamin D3 metabolites and further metabolism of C-3 epimers. J Biol Chem. 2004;279(16):15897–907. doi:10.1074/jbc.M311473200.PubMedCrossRef

65.

Brown AJ, Ritter C, Slatopolsky E, Muralidharan KR, Okamura WH, Reddy GS. 1α,25-Dihydroxy-3-Epi-vitamin D3, a natural metabolite of 1α,25-dihydroxyvitamin D3, is a potent suppressor of parathyroid hormone secretion. J Cell Biochem. 1999;73(1):106–13. doi:10.1002/(sici)1097-4644(19990401)73:1<106::aid-jcb12>3.0.co;2-q.PubMedCrossRef

66.

Fleet JC, Bradley J, Reddy GS, Ray R, Wood RJ. 1 alpha,25-(OH)2-vitamin D3 analogs with minimal in vivo calcemic activity can stimulate significant transepithelial calcium transport and mRNA expression in vitro. Arch Biochem Biophys. 1996;329(2):228–34. doi:10.1006/abbi.1996.0213.

67.

Singh RJ, Taylor RL, Reddy GS, Grebe SK. 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. J Clin Endocrinol Metab. 2006;91(8):3055–61. doi:10.1210/jc.2006-0710.PubMedCrossRef

68.

Stepman HC, Vanderroost A, Stockl D, Thienpont LM. Full-scan mass spectral evidence for 3-epi-25-hydroxyvitamin D in serum of infants and adults. Clin Chem Lab Med. 2011;49(2):253–6. doi:10.1515/CCLM.2011.050.PubMedCrossRef

69.

van den Ouweland JMW, Beijers AM, van Daal H. Fast separation of 25-hydroxyvitamin D3 from 3-Epi-25-hydroxyvitamin D3 in human serum by liquid chromatography–tandem mass spectrometry: variable prevalence of 3-Epi-25-hydroxyvitamin D3 in infants, children, and adults. Clin Chem. 2011;57(11):1618–9. doi:10.1373/clinchem.2011.170282.PubMedCrossRef

70.

Lensmeyer GL, Wiebe DA, Binkley N, Drezner MK. HPLC method for 25-hydroxyvitamin D measurement: comparison with contemporary assays. Clin Chem. 2006;52(6):1120–6. doi:10.1373/clinchem.2005.064956.

71.

Schleicher RL, Encisco SE, Chaudhary-Webb M, Paliakov E, McCoy LF, Pfeiffer CM. 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. Clin Chim Acta. 2011;412(17–18):1594–9. doi:10.1016/j.cca.2011.05.010.

72.

Keevil B. Does the presence of 3-epi-25OHD(3) affect the routine measurement of vitamin D using liquid chromatography tandem mass spectrometry? Clin Chem Lab Med. 2011. doi:10.1515/CCLM.2011.755.

73.

Lensmeyer G, Poquette M, Wiebe D, Binkley N. The C-3 epimer of 25-hydroxyvitamin D3 is present in adult serum. J Clin Endocrinol Metab. 2012;97(1):163–8. doi:10.1210/jc.2011-0584.PubMedCrossRef

74.

Strathmann FG, Sadilkova K, Laha TJ, Lesourd SE, Bornhorst JA, Hoofnagle AN, et al. 3-epi-25 hydroxyvitamin D concentrations are not correlated with age in a cohort of infants and adults. Clin Chim Acta. 2012;413(1–2):203–6. doi:10.1016/j.cca.2011.09.028.PubMedCrossRef

75.

Baecher S, Leinenbach A, Wright JA, Pongratz S, Kobold U, Thiele R. Simultaneous quantification of four vitamin D metabolites in human serum using high performance liquid chromatography tandem mass spectrometry for vitamin D profiling. Clin Biochem. 2012. doi:10.1016/j.clinbiochem.2012.06.030.

76.

Reddy GS, Tserng KY. Calcitroic acid, end product of renal metabolism of 1,25-dihydroxyvitamin D3 through the C-24 oxidation pathway. Biochemistry. 1989;28(4):1763–9. doi:10.1021/bi00430a051.PubMedCrossRef

77.

St-Arnaud R, Arabian A, Travers R, Barletta F, Raval-Pandya M, Chapin K, et al. Deficient mineralization of intramembranous bone in vitamin D-24-hydroxylase-ablated mice is Due to elevated 1,25-dihydroxyvitamin D and Not to the absence of 24,25-dihydroxyvitamin D. Endocrinology. 2000;141(7):2658–66. doi:10.1210/en.141.7.2658.PubMedCrossRef

78.

Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, John U, et al. Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med. 2011;365(5):410–21. doi:10.1056/NEJMoa1103864.

79.

Dauber A, Nguyen TT, Sochett E, Cole DE, Horst R, Abrams SA, et al. Genetic defect in CYP24A1, the vitamin D 24-hydroxylase gene, in a patient with severe infantile hypercalcemia. J Clin Endocrinol Metab. 2012;97(2):E268–74. doi:10.1210/jc.2011-1972.

80.

Arnaud CD. Biochemical markers of bone turnover for predicting BMD in early postmenopausal women. J Clin Endocrinol Metab. 1998;83(3):1044-a–1045. doi:10.1210/jc.83.3.1044-a.CrossRef

81.

Nakamura T, Kurokawa T, Orimo H. Increase of bone volume in vitamin D-repleted rats by massive administration of 24R,25(OH)2D3. Calcif Tissue Int. 1988;43(4):235–43.PubMedCrossRef

82.

Nakamura T, Kurokawa T, Orimo H. Increased mechanical strength of the vitamin D-replete rat femur by the treatment with a large dose of 24R,25(OH)2D3. Bone. 1989;10(2):117–23.PubMedCrossRef

83.

Wagner D, Hanwell HE, Schnabl K, Yazdanpanah M, Kimball S, Fu L, et al. The ratio of serum 24,25-dihydroxyvitamin D(3) to 25-hydroxyvitamin D(3) is predictive of 25-hydroxyvitamin D(3) response to vitamin D(3) supplementation. J Steroid Biochem Mol Biol. 2011;126(3–5):72–7. doi:10.1016/j.jsbmb.2011.05.003.

84.

Horst RL, Littledike ET, Gray RW, Napoli JL. Impaired 24,25-dihydroxyvitamin D production in anephric human and pig. J Clin Invest. 1981;67(1):274–80. doi:10.1172/JCI110023.

85.

Edouard T, Husseini A, Glorieux FH, Rauch F. Serum 24,25-dihydroxyvitamin D concentrations in osteogenesis imperfecta: relationship to bone parameters. J Clin Endocrinol Metab. 2012;97(4):1243–9. doi:10.1210/jc.2011-3015.PubMedCrossRef

86.

Tanaka Y, Frank H, DeLuca HF, Koizumi N, Ikekawa N. Importance of the stereochemical position of the 24-hydroxyl to biological activity of 24-hydroxyvitamin D3. Biochemistry. 1975;14(15):3293–6. doi:10.1021/bi00686a001.PubMedCrossRef

87.

Tsugawa N, Suhara Y, Kamao M, Okano T. Determination of 25-hydroxyvitamin D in human plasma using high-performance liquid chromatography-tandem mass spectrometry. Anal Chem. 2005;77(9):3001–7. doi:10.1021/ac048249c.

88.

Higashi T, Awada D, Shimada K. Determination of 24,25-dihydroxyvitamin D(3) in human plasma using liquid chromatography-mass spectrometry after derivatization with a Cookson-type reagent. Biomed Chromatogr. 2001;15(2):133–40. doi:10.1002/bmc.43.

89.

Bouillon R, Okamura WH, Norman AW. Structure-function relationships in the vitamin D endocrine system. Endocr Rev. 1995;16(2):200–57. doi:10.1210/edrv-16-2-200.PubMed

90.

Brown AJ, Slatopolsky E. Vitamin D analogs: therapeutic applications and mechanisms for selectivity. Mol Asp Med. 2008;29(6):433–52. doi:10.1016/j.mam.2008.04.001.CrossRef

91.

Sauter G, Berr F, Beuers U, Fischer S, Paumgartner G. Serum concentrations of 7alpha-hydroxy-4-cholesten-3-one reflect bile acid synthesis in humans. Hepatology. 1996;24(1):123–6. doi:10.1053/jhep.1996.v24.pm0008707250.

92.

Shiraishi A, Higashi S, Ohkawa H, Kubodera N, Hirasawa T, Ezawa I, et al. The advantage of alfacalcidol over vitamin D in the treatment of osteoporosis. Calcif Tissue Int. 1999;65(4):311–6.

93.

Napoli JL, Pramanik BC, Partridge JJ, Uskokovic MR, Horst RL. 23S,25-dihydroxyvitamin D3 as a circulating metabolite of vitamin D3. Its role in 25-hydroxyvitamin D3-26,23-lactone biosynthesis. J Biol Chem. 1982;257(16):9634–9.

94.

Wichmann JK, DeLuca HF, Schnoes HK, Horst RL, Shepard RM, Jorgensen NA. 25-Hydroxyvitamin D3 26,23-lactone: a new in vivo metabolite of vitamin D. Biochemistry. 1979;18(22):4775–80.

95.

Chace DH, Kalas TA, Naylor EW. The application of tandem mass spectrometry to neonatal screening for inherited disorders of intermediary metabolism. [Review]. Annu Rev Genomics Hum Genet. 2002;3:17–45. doi:10.1146/annurev.genom.3.022502.103213.PubMedCrossRef

96.

Eyles D, Anderson C, Ko P, Jones A, Thomas A, Burne T, et al. A sensitive LC/MS/MS assay of 25OH vitamin D3 and 25OH vitamin D2 in dried blood spots. Clin Chim Acta. 2009;403(1–2):145–51. doi:10.1016/j.cca.2009.02.005.

97.

Newman MS, Brandon TR, Groves MN, Gregory WL, Kapur S, Zava DT. A liquid chromatography/tandem mass spectrometry method for determination of 25-hydroxy vitamin D2 and 25-hydroxy vitamin D3 in dried blood spots: a potential adjunct to diabetes and cardiometabolic risk screening. J Diabetes Sci Technol. 2009;3(1):156–62.PubMed

98.

Hollis BW, Wagner CL. Vitamin D deficiency during pregnancy: an ongoing epidemic. [Comment Editorial]. Am J Clin Nutr. 2006;84(2):273.PubMed

99.

Ekins R. Measurement of free hormones in blood. [Review]. Endocr Rev. 1990;11(1):5–46.PubMedCrossRef

100.

Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG. Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab. 1986;63(4):954–9.

101.

van Hoof HJC, Swinkels LMJW, Ross HA, Sweep CGJ, Benraad TJ. Determination of Non-protein-bound plasma 1,25-dihydroxyvitamin D by symmetric (rate) dialysis. Anal Biochem. 1998;258(2):176–83. doi:10.1006/abio.1998.2586.PubMedCrossRef

102.

Gröschl M. Current status of salivary hormone analysis. Clin Chem. 2008;54(11):1759–69. doi:10.1373/clinchem.2008.108910.PubMedCrossRef

103.

Fairney A, Saphier PW. Studies on the measurement of 25-hydroxy vitamin D in human saliva. Br J Nutr. 1987;57(1):13–25.PubMedCrossRef

104.

Holmoy T, Moen SM, Gundersen TA, Holick MF, Fainardi E, Castellazzi M, et al. 25-hydroxyvitamin D in cerebrospinal fluid during relapse and remission of multiple sclerosis. Mult Scler. 2009;15(11):1280–5. doi:10.1177/1352458509107008.PubMedCrossRef

105.

Sempos CT, Vesper HW, Phinney KW, Thienpont LM, Coates PM. Vitamin D status as an international issue: national surveys and the problem of standardization. Scand J Clin Lab Invest Suppl. 2012;243:32–40. doi:10.3109/00365513.2012.681935.PubMed

106.

Phinney KW. Development of a standard reference material for vitamin D in serum. [Review]. Am J Clin Nutr. 2008;88(2):511S–2S.PubMed

107.

Phinney K, Bedner M, Tai SS, Vamathevan V, Sander LC, Sharpless KE, et al. Development and certification of a standard reference material for vitamin D metabolites in human serum. Anal Chem. 2011. doi:10.1021/ac202047n.

108.

Certificate of analysis, Standard Reference Material 2972: 25-hydroxyvitamin D2 and D3 calibration solutions. Gaithersburg, MD: Standard Reference Materials Program, NIST (2009).

109.

Carter GD. 25-Hydroxyvitamin D assays: the quest for accuracy. Clin Chem. 2009;55(7):1300–2. doi:10.1373/clinchem.2009.125906.PubMedCrossRef

110.

Yates AM, Bowron A, Calton L, Heynes J, Field H, Rainbow S, et al. Interlaboratory variation in 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 is significantly improved if common calibration material is used. Clin Chem. 2008;54(12):2082–4. doi:10.1373/clinchem.2008.110452.PubMedCrossRef

111.

Carter GD, Jones JC. Use of a common standard improves the performance of liquid chromatography-tandem mass spectrometry methods for serum 25-hydroxyvitamin-D. Ann Clin Biochem. 2009;46(1):79–81. doi:10.1258/acb.2008.008135.PubMedCrossRef

112.

Carter GD. Accuracy of 25-hydroxyvitamin D assays: confronting the issues. [Review]. Curr Drug Targets. 2011;12(1):19–28.PubMedCrossRef

113.

Janssen MJW, Wielders JPM, Bekker CC, Boesten LSM, Buijs MM, Heijboer AC, et al. Multicenter comparison study of current methods to measure 25-hydroxyvitamin D in serum. Steroids. doi:10.1016/j.steroids.2012.07.013.

114.

Heijboer AC, Blankenstein MA, Kema IP, Buijs MM. Accuracy of 6 routine 25-hydroxyvitamin D assays: influence of vitamin D binding protein concentration. Clin Chem. 2012;58(3):543–8. doi:10.1373/clinchem.2011.176545.PubMedCrossRef

115.

Liel Y, Ulmer E, Shary J, Hollis BW, Bell NH. Low circulating vitamin D in obesity. Calcif Tissue Int. 1988;43(4):199–201.

116.

Higashi T, Yamauchi A, Shimada K. Application of 4-(4-nitrophenyl)-1,2,4-triazoline-3,5-dione to analysis of 25-hydroxyvitamin D<SUB>3</SUB>in human plasma by liquid chromatography/electron capture atmospheric pressure chemical ionization-mass spectrometry. Anal Sci. 2003;19(6):941–3.PubMedCrossRef

117.

Gören AC, Bilsel G, Bilsel M. Rapid and simultaenous determination of 25-OH-vitamin D2 and D3 in human serum by LC/MS/MS: validation and uncertainty assessment. J Chem Metrl. 2007;1(1):1–9.CrossRef

118.

Priego Capote F, Jiménez JR, Granados JMM, de Castro MDL. Identification and determination of fat-soluble vitamins and metabolites in human serum by liquid chromatography/triple quadrupole mass spectrometry with multiple reaction monitoring. Rapid Commun Mass Spectrom. 2007;21(11):1745–54. doi:10.1002/rcm.3014.PubMedCrossRef

119.

Xie W, Chavez-Eng CM, Fang W, Constanzer ML, Matuszewski BK, Mullett WM, et al. Quantitative liquid chromatographic and tandem mass spectrometric determination of vitamin D3 in human serum with derivatization: a comparison of in-tube LLE, 96-well plate LLE and in-tip SPME. J Chromatogr B Anal Technol Biomed Life Sci. 2011;879(17–18):1457–66. doi:10.1016/j.jchromb.2011.03.018.

Title: Vitamin D and metabolites measurement by tandem mass spectrometry
Authors: Johannes M. W. van den Ouweland
Michael Vogeser
Silvia Bächer
Publication date: 01-06-2013
Publisher: Springer US
Published in: Reviews in Endocrine and Metabolic Disorders / Issue 2/2013
Print ISSN: 1389-9155
Electronic ISSN: 1573-2606
DOI: https://doi.org/10.1007/s11154-013-9241-0

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2013

The role of endothelial insulin signaling in the regulation of glucose metabolism

The use of mass spectrometry to improve the diagnosis and the management of the HPA axis

Pathophysiology of GHRH-growth hormone-IGF1 axis in HIV/AIDS

Insights into tandem mass spectrometry for the laboratory endocrinology

Bone and vitamin D metabolism in HIV

Human immune deficiency virus (HIV) infection and the hypothalamic pituitary adrenal axis

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage