Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis |
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| Authors: | Akiko Nagata Kazuto Iijima Ryota Sakamoto Yuka Mizumoto Miho Iwaki Masaki Takiwaki Yoshikuni Kikutani Seketsu Fukuzawa Minami Odagi Masayuki Tera Kazuo Nagasawa |
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| Institution: | 1.Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan; (A.N.); (K.I.); (R.S.); (Y.M.); (M.I.); (M.O.); (M.T.);2.Medical Equipment Business Operations, Management Strategy Planning Division, JEOL Ltd., Akishima, Tokyo 196-8558, Japan; (M.T.); (Y.K.); (S.F.) |
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| Abstract: | Blood levels of the vitamin D3 (D3) metabolites 25-hydroxyvitamin D3 (25(OH)D3), 24R,25-dihydroxyvitamin D3, and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) are recognized indicators for the diagnosis of bone metabolism-related diseases, D3 deficiency-related diseases, and hypercalcemia, and are generally measured by liquid-chromatography tandem mass spectrometry (LC-MS/MS) using an isotope dilution method. However, other D3 metabolites, such as 20-hydroxyvitamin D3 and lactone D3, also show interesting biological activities and stable isotope-labeled derivatives are required for LC-MS/MS analysis of their concentrations in serum. Here, we describe a versatile synthesis of deuterium-labeled D3 metabolites using A-ring synthons containing three deuterium atoms. Deuterium-labeled 25(OH)D3 (2), 25(OH)D3-23,26-lactone (6), and 1,25(OH)2D3-23,26-lactone (7) were synthesized, and successfully applied as internal standards for the measurement of these compounds in pooled human serum. This is the first quantification of 1,25(OH)2D3-23,26-lactone (7) in human serum. |
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| Keywords: | vitamin D deuterium labeling liquid-chromatography tandem mass spectrometry measurement of vitamin D metabolites in blood |
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