Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis
Blood levels of the vitamin D<sub>3</sub> (D<sub>3</sub>) metabolites 25-hydroxyvitamin D<sub>3</sub> (25(OH)D<sub>3</sub>), 24<i>R</i>,25-dihydroxyvitamin D<sub>3</sub>, and 1α,25-dihydroxyvitamin D<sub>3</sub> (1,2...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/8/2427 |
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| author | Akiko Nagata Kazuto Iijima Ryota Sakamoto Yuka Mizumoto Miho Iwaki Masaki Takiwaki Yoshikuni Kikutani Seketsu Fukuzawa Minami Odagi Masayuki Tera Kazuo Nagasawa |
| author_facet | Akiko Nagata Kazuto Iijima Ryota Sakamoto Yuka Mizumoto Miho Iwaki Masaki Takiwaki Yoshikuni Kikutani Seketsu Fukuzawa Minami Odagi Masayuki Tera Kazuo Nagasawa |
| author_sort | Akiko Nagata |
| collection | DOAJ |
| description | Blood levels of the vitamin D<sub>3</sub> (D<sub>3</sub>) metabolites 25-hydroxyvitamin D<sub>3</sub> (25(OH)D<sub>3</sub>), 24<i>R</i>,25-dihydroxyvitamin D<sub>3</sub>, and 1α,25-dihydroxyvitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>) are recognized indicators for the diagnosis of bone metabolism-related diseases, D<sub>3</sub> 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 D<sub>3</sub> metabolites, such as 20-hydroxyvitamin D<sub>3</sub> and lactone D<sub>3</sub>, 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 D<sub>3</sub> metabolites using A-ring synthons containing three deuterium atoms. Deuterium-labeled 25(OH)D<sub>3</sub> (<b>2</b>), 25(OH)D<sub>3</sub>-23,26-lactone (<b>6</b>), and 1,25(OH)<sub>2</sub>D<sub>3</sub>-23,26-lactone (<b>7</b>) 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)<sub>2</sub>D<sub>3</sub>-23,26-lactone (<b>7</b>) in human serum. |
| first_indexed | 2024-03-09T10:31:31Z |
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| id | doaj.art-d2238d20565c4872998ea88502ec583d |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T10:31:31Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-d2238d20565c4872998ea88502ec583d2023-12-01T21:15:53ZengMDPI AGMolecules1420-30492022-04-01278242710.3390/molecules27082427Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS AnalysisAkiko Nagata0Kazuto Iijima1Ryota Sakamoto2Yuka Mizumoto3Miho Iwaki4Masaki Takiwaki5Yoshikuni Kikutani6Seketsu Fukuzawa7Minami Odagi8Masayuki Tera9Kazuo Nagasawa10Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, JapanDepartment of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, JapanDepartment of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, JapanDepartment of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, JapanDepartment of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, JapanMedical Equipment Business Operations, Management Strategy Planning Division, JEOL Ltd., Akishima, Tokyo 196-8558, JapanMedical Equipment Business Operations, Management Strategy Planning Division, JEOL Ltd., Akishima, Tokyo 196-8558, JapanMedical Equipment Business Operations, Management Strategy Planning Division, JEOL Ltd., Akishima, Tokyo 196-8558, JapanDepartment of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, JapanDepartment of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, JapanDepartment of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, JapanBlood levels of the vitamin D<sub>3</sub> (D<sub>3</sub>) metabolites 25-hydroxyvitamin D<sub>3</sub> (25(OH)D<sub>3</sub>), 24<i>R</i>,25-dihydroxyvitamin D<sub>3</sub>, and 1α,25-dihydroxyvitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>) are recognized indicators for the diagnosis of bone metabolism-related diseases, D<sub>3</sub> 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 D<sub>3</sub> metabolites, such as 20-hydroxyvitamin D<sub>3</sub> and lactone D<sub>3</sub>, 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 D<sub>3</sub> metabolites using A-ring synthons containing three deuterium atoms. Deuterium-labeled 25(OH)D<sub>3</sub> (<b>2</b>), 25(OH)D<sub>3</sub>-23,26-lactone (<b>6</b>), and 1,25(OH)<sub>2</sub>D<sub>3</sub>-23,26-lactone (<b>7</b>) 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)<sub>2</sub>D<sub>3</sub>-23,26-lactone (<b>7</b>) in human serum.https://www.mdpi.com/1420-3049/27/8/2427vitamin Ddeuterium labelingliquid-chromatography tandem mass spectrometrymeasurement of vitamin D metabolites in blood |
| spellingShingle | Akiko Nagata Kazuto Iijima Ryota Sakamoto Yuka Mizumoto Miho Iwaki Masaki Takiwaki Yoshikuni Kikutani Seketsu Fukuzawa Minami Odagi Masayuki Tera Kazuo Nagasawa Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis Molecules vitamin D deuterium labeling liquid-chromatography tandem mass spectrometry measurement of vitamin D metabolites in blood |
| title | Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis |
| title_full | Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis |
| title_fullStr | Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis |
| title_full_unstemmed | Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis |
| title_short | Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis |
| title_sort | synthesis of deuterium labeled vitamin d metabolites as internal standards for lc ms analysis |
| topic | vitamin D deuterium labeling liquid-chromatography tandem mass spectrometry measurement of vitamin D metabolites in blood |
| url | https://www.mdpi.com/1420-3049/27/8/2427 |
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