A validated LC-MS/MS assay for quantification of 24(S)-hydroxycholesterol in plasma and cerebrospinal fluid
24(S)-hydroxycholesterol [24(S)-HC] is a cholesterol metabolite that is formed almost exclusively in the brain. The concentrations of 24(S)-HC in cerebrospinal fluid (CSF) and/or plasma might be a sensitive marker of altered cholesterol metabolism in the CNS. A highly sensitive 2D-LC-MS/MS assay was...
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doaj-ff24b5d87b0d410f9097303d737e64912021-04-28T05:57:54ZengElsevierJournal of Lipid Research0022-22752015-06-0156612221233A validated LC-MS/MS assay for quantification of 24(S)-hydroxycholesterol in plasma and cerebrospinal fluidRohini Sidhu0Hui Jiang1Nicole Y. Farhat2Nuria Carrillo-Carrasco3Myra Woolery4Elizabeth Ottinger5Forbes D. Porter6Jean E. Schaffer7Daniel S. Ory8Xuntian Jiang9Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO 63110Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO 63110Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892Therapeutics for Rare and Neglected Diseases National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850Nursing Department, National Institutes of Health, Bethesda, MD 20892Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO 63110Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO 63110To whom correspondence should be addressed.; Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO 6311024(S)-hydroxycholesterol [24(S)-HC] is a cholesterol metabolite that is formed almost exclusively in the brain. The concentrations of 24(S)-HC in cerebrospinal fluid (CSF) and/or plasma might be a sensitive marker of altered cholesterol metabolism in the CNS. A highly sensitive 2D-LC-MS/MS assay was developed for the quantification of 24(S)-HC in human plasma and CSF. In the development of an assay for 24(S)-HC in CSF, significant nonspecific binding of 24(S)-HC was observed and resolved with the addition of 2.5% 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) into CSF samples. The sample preparation consists of liquid-liquid extraction with methyl-tert-butyl ether and derivatization with nicotinic acid. Good linearity was observed in a range from 1 to 200 ng/ml and from 0.025 to 5 ng/ml, for plasma and CSF, respectively. Acceptable precision and accuracy were obtained for concentrations over the calibration curve ranges. Stability of 24(S)-HC was reported under a variety of storage conditions. This method has been successfully applied to support a National Institutes of Health-sponsored clinical trial of HP-β-CD in Niemann-Pick type C1 patients, in which 24(S)-HC is used as a pharmacodynamic biomarker.http://www.sciencedirect.com/science/article/pii/S0022227520317326two-dimensional liquid chromatography-tandem mass spectrometryvalidationNiemann-Pick C1 disease2-hydroxypropyl-β-cyclodextrin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rohini Sidhu Hui Jiang Nicole Y. Farhat Nuria Carrillo-Carrasco Myra Woolery Elizabeth Ottinger Forbes D. Porter Jean E. Schaffer Daniel S. Ory Xuntian Jiang |
spellingShingle |
Rohini Sidhu Hui Jiang Nicole Y. Farhat Nuria Carrillo-Carrasco Myra Woolery Elizabeth Ottinger Forbes D. Porter Jean E. Schaffer Daniel S. Ory Xuntian Jiang A validated LC-MS/MS assay for quantification of 24(S)-hydroxycholesterol in plasma and cerebrospinal fluid Journal of Lipid Research two-dimensional liquid chromatography-tandem mass spectrometry validation Niemann-Pick C1 disease 2-hydroxypropyl-β-cyclodextrin |
author_facet |
Rohini Sidhu Hui Jiang Nicole Y. Farhat Nuria Carrillo-Carrasco Myra Woolery Elizabeth Ottinger Forbes D. Porter Jean E. Schaffer Daniel S. Ory Xuntian Jiang |
author_sort |
Rohini Sidhu |
title |
A validated LC-MS/MS assay for quantification of 24(S)-hydroxycholesterol in plasma and cerebrospinal fluid |
title_short |
A validated LC-MS/MS assay for quantification of 24(S)-hydroxycholesterol in plasma and cerebrospinal fluid |
title_full |
A validated LC-MS/MS assay for quantification of 24(S)-hydroxycholesterol in plasma and cerebrospinal fluid |
title_fullStr |
A validated LC-MS/MS assay for quantification of 24(S)-hydroxycholesterol in plasma and cerebrospinal fluid |
title_full_unstemmed |
A validated LC-MS/MS assay for quantification of 24(S)-hydroxycholesterol in plasma and cerebrospinal fluid |
title_sort |
validated lc-ms/ms assay for quantification of 24(s)-hydroxycholesterol in plasma and cerebrospinal fluid |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2015-06-01 |
description |
24(S)-hydroxycholesterol [24(S)-HC] is a cholesterol metabolite that is formed almost exclusively in the brain. The concentrations of 24(S)-HC in cerebrospinal fluid (CSF) and/or plasma might be a sensitive marker of altered cholesterol metabolism in the CNS. A highly sensitive 2D-LC-MS/MS assay was developed for the quantification of 24(S)-HC in human plasma and CSF. In the development of an assay for 24(S)-HC in CSF, significant nonspecific binding of 24(S)-HC was observed and resolved with the addition of 2.5% 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) into CSF samples. The sample preparation consists of liquid-liquid extraction with methyl-tert-butyl ether and derivatization with nicotinic acid. Good linearity was observed in a range from 1 to 200 ng/ml and from 0.025 to 5 ng/ml, for plasma and CSF, respectively. Acceptable precision and accuracy were obtained for concentrations over the calibration curve ranges. Stability of 24(S)-HC was reported under a variety of storage conditions. This method has been successfully applied to support a National Institutes of Health-sponsored clinical trial of HP-β-CD in Niemann-Pick type C1 patients, in which 24(S)-HC is used as a pharmacodynamic biomarker. |
topic |
two-dimensional liquid chromatography-tandem mass spectrometry validation Niemann-Pick C1 disease 2-hydroxypropyl-β-cyclodextrin |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520317326 |
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