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Deep mining of oxysterols and cholestenoic acids in human plasma and cerebrospinal fluid: Quantification using isotope dilution mass spectrometry

Eylan Yutuc Orcid Logo, Alison Dickson, Manuela Pacciarini, Lauren Griffiths Orcid Logo, Paul R.S. Baker, Lisa Connell, Anders Öhman, Lars Forsgren, Miles Trupp, Sílvia Vilarinho, Youssef Khalil, Peter T. Clayton, Sinan Sari, Buket Dalgic, Philip Höflinger, Ludger Schöls, William Griffiths Orcid Logo, Yuqin Wang Orcid Logo

Analytica Chimica Acta, Volume: 1154, Start page: 338259

Swansea University Authors: Eylan Yutuc Orcid Logo, Alison Dickson, Manuela Pacciarini, Lauren Griffiths Orcid Logo, William Griffiths Orcid Logo, Yuqin Wang Orcid Logo

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Abstract

Both plasma and cerebrospinal fluid (CSF) are rich in cholesterol and its metabolites. Here we describe in detail a methodology for the identification and quantification of multiple sterols including oxysterols and sterol-acids found in these fluids. The method is translatable to any laboratory with...

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Published in: Analytica Chimica Acta
ISSN: 0003-2670
Published: Elsevier BV 2021
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Here we describe in detail a methodology for the identification and quantification of multiple sterols including oxysterols and sterol-acids found in these fluids. The method is translatable to any laboratory with access to liquid chromatography &#x2013; tandem mass spectrometry. The method exploits isotope-dilution mass spectrometry for absolute quantification of target metabolites. The method is applicable for semi-quantification of other sterols for which isotope labelled surrogates are not available and approximate quantification of partially identified sterols. Values are reported for non-esterified sterols in the absence of saponification and total sterols following saponification. In this way absolute quantification data is reported for 17 sterols in the NIST SRM 1950 plasma along with semi-quantitative data for 8 additional sterols and approximate quantification for one further sterol. 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spelling 2022-10-27T11:48:28.1599032 v2 56163 2021-02-02 Deep mining of oxysterols and cholestenoic acids in human plasma and cerebrospinal fluid: Quantification using isotope dilution mass spectrometry 99332f073ce913a9b7d8b6441b17516d 0000-0001-9971-1950 Eylan Yutuc Eylan Yutuc true false 82dc4360769527a5f3a0cd9d85cdff40 Alison Dickson Alison Dickson true false 97e7258d0fe568df57f24c043f5f90cb Manuela Pacciarini Manuela Pacciarini true false 8811c280da03bf66352d97f756e91ae1 0000-0002-8713-3687 Lauren Griffiths Lauren Griffiths true false 3316b1d1b524be1831790933eed1c26e 0000-0002-4129-6616 William Griffiths William Griffiths true false c92729b58622f9fdf6a0e7d8f4ce5081 0000-0002-3063-3066 Yuqin Wang Yuqin Wang true false 2021-02-02 BMS Both plasma and cerebrospinal fluid (CSF) are rich in cholesterol and its metabolites. Here we describe in detail a methodology for the identification and quantification of multiple sterols including oxysterols and sterol-acids found in these fluids. The method is translatable to any laboratory with access to liquid chromatography – tandem mass spectrometry. The method exploits isotope-dilution mass spectrometry for absolute quantification of target metabolites. The method is applicable for semi-quantification of other sterols for which isotope labelled surrogates are not available and approximate quantification of partially identified sterols. Values are reported for non-esterified sterols in the absence of saponification and total sterols following saponification. In this way absolute quantification data is reported for 17 sterols in the NIST SRM 1950 plasma along with semi-quantitative data for 8 additional sterols and approximate quantification for one further sterol. In a pooled (CSF) sample used for internal quality control, absolute quantification was performed on 10 sterols, semi-quantification on 9 sterols and approximate quantification on a further three partially identified sterols. The value of the method is illustrated by confirming the sterol phenotype of a patient suffering from ACOX2 deficiency, a rare disorder of bile acid biosynthesis, and in a plasma sample from a patient suffering from cerebrotendinous xanthomatosis, where cholesterol 27-hydroxylase is deficient. Journal Article Analytica Chimica Acta 1154 338259 Elsevier BV 0003-2670 Cholesterol; Hydroxycholesterol; Cholestenoic acid; Bile acid; LC-MS; Derivatisation; Isotope-labelled standard 15 4 2021 2021-04-15 10.1016/j.aca.2021.338259 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University UKRI, BB/S019588/1 2022-10-27T11:48:28.1599032 2021-02-02T08:38:59.6197900 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Eylan Yutuc 0000-0001-9971-1950 1 Alison Dickson 2 Manuela Pacciarini 3 Lauren Griffiths 0000-0002-8713-3687 4 Paul R.S. Baker 5 Lisa Connell 6 Anders Öhman 7 Lars Forsgren 8 Miles Trupp 9 Sílvia Vilarinho 10 Youssef Khalil 11 Peter T. Clayton 12 Sinan Sari 13 Buket Dalgic 14 Philip Höflinger 15 Ludger Schöls 16 William Griffiths 0000-0002-4129-6616 17 Yuqin Wang 0000-0002-3063-3066 18 56163__19373__f1abe01cd4994a419f7655ec5a398d5e.pdf 56163.pdf 2021-02-26T09:31:42.0175449 Output 6179588 application/pdf Version of Record true © 2021 The Author(s). This is an open access article under the CC BY license true eng http://creativecommons.org/licenses/by/4.0/
title Deep mining of oxysterols and cholestenoic acids in human plasma and cerebrospinal fluid: Quantification using isotope dilution mass spectrometry
spellingShingle Deep mining of oxysterols and cholestenoic acids in human plasma and cerebrospinal fluid: Quantification using isotope dilution mass spectrometry
Eylan Yutuc
Alison Dickson
Manuela Pacciarini
Lauren Griffiths
William Griffiths
Yuqin Wang
title_short Deep mining of oxysterols and cholestenoic acids in human plasma and cerebrospinal fluid: Quantification using isotope dilution mass spectrometry
title_full Deep mining of oxysterols and cholestenoic acids in human plasma and cerebrospinal fluid: Quantification using isotope dilution mass spectrometry
title_fullStr Deep mining of oxysterols and cholestenoic acids in human plasma and cerebrospinal fluid: Quantification using isotope dilution mass spectrometry
title_full_unstemmed Deep mining of oxysterols and cholestenoic acids in human plasma and cerebrospinal fluid: Quantification using isotope dilution mass spectrometry
title_sort Deep mining of oxysterols and cholestenoic acids in human plasma and cerebrospinal fluid: Quantification using isotope dilution mass spectrometry
author_id_str_mv 99332f073ce913a9b7d8b6441b17516d
82dc4360769527a5f3a0cd9d85cdff40
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8811c280da03bf66352d97f756e91ae1
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c92729b58622f9fdf6a0e7d8f4ce5081
author_id_fullname_str_mv 99332f073ce913a9b7d8b6441b17516d_***_Eylan Yutuc
82dc4360769527a5f3a0cd9d85cdff40_***_Alison Dickson
97e7258d0fe568df57f24c043f5f90cb_***_Manuela Pacciarini
8811c280da03bf66352d97f756e91ae1_***_Lauren Griffiths
3316b1d1b524be1831790933eed1c26e_***_William Griffiths
c92729b58622f9fdf6a0e7d8f4ce5081_***_Yuqin Wang
author Eylan Yutuc
Alison Dickson
Manuela Pacciarini
Lauren Griffiths
William Griffiths
Yuqin Wang
author2 Eylan Yutuc
Alison Dickson
Manuela Pacciarini
Lauren Griffiths
Paul R.S. Baker
Lisa Connell
Anders Öhman
Lars Forsgren
Miles Trupp
Sílvia Vilarinho
Youssef Khalil
Peter T. Clayton
Sinan Sari
Buket Dalgic
Philip Höflinger
Ludger Schöls
William Griffiths
Yuqin Wang
format Journal article
container_title Analytica Chimica Acta
container_volume 1154
container_start_page 338259
publishDate 2021
institution Swansea University
issn 0003-2670
doi_str_mv 10.1016/j.aca.2021.338259
publisher Elsevier BV
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description Both plasma and cerebrospinal fluid (CSF) are rich in cholesterol and its metabolites. Here we describe in detail a methodology for the identification and quantification of multiple sterols including oxysterols and sterol-acids found in these fluids. The method is translatable to any laboratory with access to liquid chromatography – tandem mass spectrometry. The method exploits isotope-dilution mass spectrometry for absolute quantification of target metabolites. The method is applicable for semi-quantification of other sterols for which isotope labelled surrogates are not available and approximate quantification of partially identified sterols. Values are reported for non-esterified sterols in the absence of saponification and total sterols following saponification. In this way absolute quantification data is reported for 17 sterols in the NIST SRM 1950 plasma along with semi-quantitative data for 8 additional sterols and approximate quantification for one further sterol. In a pooled (CSF) sample used for internal quality control, absolute quantification was performed on 10 sterols, semi-quantification on 9 sterols and approximate quantification on a further three partially identified sterols. The value of the method is illustrated by confirming the sterol phenotype of a patient suffering from ACOX2 deficiency, a rare disorder of bile acid biosynthesis, and in a plasma sample from a patient suffering from cerebrotendinous xanthomatosis, where cholesterol 27-hydroxylase is deficient.
published_date 2021-04-15T04:10:55Z
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