Determination of Vitamin D and Its Metabolites in Human Brain Using an Ultra-Pressure LC-Tandem Mass Spectra Method
Autor: | Thomas Holland, Gregory G. Dolnikowski, Tong Zheng, Xueyan Fu, Sarah L. Booth, Bess Dawson-Hughes, Martha Clare Morris, William B. Patterson |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Vitamin Postmortem studies brain Medicine (miscellaneous) vitamin D Corpus callosum 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Vitamin D and neurology medicine Prefrontal cortex metabolites quadrupole ion trap Temporal cortex 030109 nutrition & dietetics Nutrition and Dietetics Chromatography Human brain medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Research Methodology/Study Design Cholecalciferol Food Science dementia |
Zdroj: | Current Developments in Nutrition |
ISSN: | 2475-2991 |
Popis: | Background Low serum total 25-hydroxyvitamin D3 [25(OH)D3] concentrations have been associated with cognitive impairment. However, it is unclear if serum 25(OH)D3 concentrations are a valid indicator of the concentrations of vitamin D and its metabolites in human brain. Objectives The aim of this study was to develop and validate a method to quantify vitamin D3, 25(OH)D3, and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in human brain. Methods The assay developments were performed using porcine brains. Liquid extraction was used in homogenized samples (∼0.1 g each) prior to analysis by LC-MS/MS with electrospray ionization following derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione. This method was then applied to the determination of vitamin D and its metabolites in a whole human brain obtained from the National Development and Research Institutes. Results The method showed good linearity of vitamin D3, 25(OH)D3, and 1,25(OH)2D3 over the physiological range (R 2 = 0.9995, 0.9968, and 0.9970, respectively). The lowest detection limit for vitamin D3, 25(OH)D3, and 1,25(OH)2D3 in porcine brain was 25, 50 and 25 pg/g, respectively. The method was successfully applied to the determination of vitamin D3 and its metabolites in the prefrontal cortex, middle frontal cortex, middle temporal cortex, cerebellum, corpus callosum, medulla, and pons of a human brain. All analyzed human brain regions contained 25(OH)D3, with corpus callosum containing 334 pg/g compared with 158 pg/g in cerebellum. 1,25(OH)2D3 was only detected in prefrontal and middle frontal cortices at a very low level. No vitamin D3 was detected in any examined areas of this single human brain. Conclusions To the best of our knowledge, this study is the first report of the measurement of concentrations of vitamin D metabolites in human brain. This validated method can be applied to postmortem studies to obtain accurate information about the presence and role of vitamin D and its metabolites in human brain and neurodegenerative diseases. |
Databáze: | OpenAIRE |
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