MALDI-MS-Based Quantitative Analysis of Bioactive Forms of Vitamin D in Biological Samples

Da-Hee Ahn; Hee-jin Kim; Seong-Min Kim; Sung-Hyun Jo; Jae-Hyun Jeong; Yun-Gon Kim

Korean Chemical Engineering Research, Vol.58, No.1, 106-112, February, 2020

DOI10.9713/kcer.2020.58.1.106 Export Citation

MALDI-MS-Based Quantitative Analysis of Bioactive Forms of Vitamin D in Biological Samples

Da-Hee Ahn, Hee-jin Kim, Seong-Min Kim, Sung-Hyun Jo, Jae-Hyun Jeong, and Yun-Gon Kim^†

Department of Chemical Engineering, Soongsil University, 369, Sangdo-ro, Dongjak-gu, Seoul, 06978, Korea

E-mail:

Analyzing vitamin D levels is important for monitoring health conditions because vitamin D deficiency is associated with various diseases such as rickets, osteomalacia, cardiovascular disorders and some cancers. However, vitamin D concentration in the blood is very low with optimal level of 75 nmol/L, making quantitative analysis difficult. The objective of this study was to develop a highly sensitive analysis method for vitamin D using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-MS). 25-hydroxyvitamin D (25(OH)D), which has been used as an indicator of vitamin D metabolites in human biofluids was chemically derivatized using a secosteroid signal enhancing tag (SecoSET) with powerful dienophile and permanent positive charge. The SecoSET-derivatized 25(OH)D provided good linearity (R2 > 0.99) and sensitivity (limit of quantitation: 11.3 fmol). Chemical derivatization of deuterated 25-hydroxyvitamin D3 (d6-25(OH)D3) with SecoSET enabled absolute quantitative analysis using MALDI-MS. The highly sensitive method could be successfully applied into monitoring of quantitative changes of bioactive vitamin D metabolites after treatment with ketoconazole to inhibit 1α-hydroxylase reaction related to vitamin D metabolism in human breast cancer cells. Taken together, we developed a MALDI-MS-based platform that could quantitatively analyze vitamin D metabolites from cell products, blood and other biofluids. This platform may be applied to monitor various diseases associated with vitamin D deficiency such as rickets, osteomalacia and breast cancer.

Keywords:Vitamin D metabolites;25-hydroxyvitamin;MALDI-MS;Chemical derivatization;Quantitative analysis

[References]

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[2] Bhan A, Rao AD, Rao DS, Endocrinol. Metab. Clin. North Am., 39(2), 321 (2010)

[3] Holick MF, N. Engl. J. Med., 2007(357), 266 (2007)

[4] Judd S, Tangpricha V, Circulation, 117(4), 503 (2008)

[5] Atoum M, Alzoughool F, Breast Cancer: Basic and Clinical Research, 11, 1-8(2017).

[6] Bikle DD, Cell Chem. Biol., 21(3), 319 (2014)

[7] Seamans KM, Cashman KD, Am. J. Clin. Nutr., 89(6), 1997S (2009)

[8] DeLuca HF, Am. J. Clin. Nutr., 80(6), 1689S (2004)

[9] Holick MF, Ann Epidemiol, 19(2), 73 (2009)

[10] van den Ouweland JM, Beijers AM, Demacker PN, van Daal H, J. Chromatogr. B, 878(15), 1163 (2010)

[11] Hedman CJ, Wiebe DA, Dey S, Plath J, Kemnitz JW, Ziegler TE, J. Chromatogr. B, 953(15), 62 (2014)

[12] Yuan C, Kosewick J, He X, Kozak M, Wang S, Rapid Commun. Mass Spectrom., 25(9), 1241 (2011)

[13] Higashi T, Yokota M, Goto A, Komatsu K, Sugiura T, Ogawa S, Satoh M, Nomura F, Mass Spectorm., 5(2), S0051 (2016)

[14] Ogawa S, Ooki S, Morohashi M, Yamagata K, Higashi T, Rapid Commun. Mass Spectrom., 27(21), 2453 (2013)

[15] Ogawa S, Kittaka H, Shinoda K, Ooki S, Nakata A, Higashi T, Biomed. Chromatogr., 30(6), 938 (2016)

[16] Higashi T, Shimada K, Biomed. Chromatogr., 31(1), e3808 (2017)

[17] Qi BL, Liu P, Wang QY, Cai WJ, Yuan BF, Feng YQ, Trac Trend. Anal. Chem., 59, 121 (2014)

[18] Aronov PA, Hall LM, Dettmer K, Stephensen CB, Hammock BD, Anal. Bioanal. Chem., 391(5), 1917 (2008)

[19] Kim KJ, Kim HJ, Park HG, Hwang CH, Sung C, Jang KS, Park SH, Kim BG, Lee YK, Yang YH, Sci. Rep., 6, 24489 (2016)

[20] Adamec J, Jannasch A, Huang J, Hohman E, Fleet JC, Peacock M, Ferruzzi MG, Martin B, Weaver CM, J. Sep. Sci., 34(1), 11 (2011)

[21] Vogeser M, Kyriatsoulis A, Huber E, Kobold U, Clin. Chem., 50(8), 1415 (2004)

[22] Kim JH, Woenker T, Adamec J, Regnier FE, Anal. Chem., 85(23), 11501 (2013)

[23] Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, J. Clin. Endocrinol. Metab., 96(7), 1911 (2011)

[24] Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B, Am. J. Clin. Nutr, 84(1), 18 (2006)

[25] Lensmeyer G, Poquette M, Wiebe D, Binkley N, J. Clin. Endocrinol. Metab., 97(1), 163 (2012)

[26] Carter G, Jones J, Shannon J, Williams E, Jones G, Kaufmann M, Sempos C, J. Steroid. Biochem. Mol. Biol., 164, 134 (2016)

[27] Keevil B, Clin. Chem. Lab. Med., 50(1), 181 (2012)

[28] Strathmann FG, Sadilkova K, Laha TJ, LeSourd SE, Bornhorst JA, Hoofnagle AN, Jack R, Clin. Chim. Acta., 413(1-2), 203 (2012)

[29] Henry HL, Best Pract. Res. Clin. Endocrinol. Metab., 25(4), 531-541(2011).

[30] Jones G, Prosser DE, Kaufmann M, J. Lipid Res., 55(1), 13 (2014)

[31] Townsend K, Banwell CM, Guy M, Colston KW, Mansi JL, Stewart PM, Campbell MJ, Hewison M, Clin. Cancer Res., 11(9), 3579 (2005)

[32] Hewison M, Zehnder D, Chakraverty R, Adams JS, Mol. Cell. Endocrinol., 215(1-2), 31 (2004)

[33] Zehnder D, Bland R, Williams MC, McNinch RW, Howie AJ, Stewart PM, Hewison M, J. Clin. Endocrinol. Metab., 86, 888 (2001)

[34] iesing D, Cordes T, Fischer D, Diedrich K, Friedrich M, Anticancer Res., 26(4A), 2755 (2006)

[35] Cordes T, Diesing D, Becker S, Fischer D, Diedrich K, Friedrich M, J. Steroid Biochem. Mol. Biol., 103(3-5), 326 (2007)

[36] Geng S, Zhou S, Glowacki J, J. Bone. Miner. Res., 26(5), 1145 (2011)

[37] Nguyen M, Boutignon H, Mallet E, Linglart A, Guillozo H, Jehan F, Garabedian M, J. Pediatr., 157(2), 296 (2010)