Liquid chromatography coupled to tandem mass spectrometry methods for the selective and sensitive determination of 24S-hydroxycholesterol, its sulfate, and/or glucuronide conjugates in plasma.
24S-hydroxycholesterol
glucuronide conjugate
liquid chromatography coupled to tandem mass spectrometry
plasma levels
sulfate conjugate
Journal
Journal of mass spectrometry : JMS
ISSN: 1096-9888
Titre abrégé: J Mass Spectrom
Pays: England
ID NLM: 9504818
Informations de publication
Date de publication:
May 2022
May 2022
Historique:
revised:
22
03
2022
received:
22
01
2021
accepted:
03
04
2022
pubmed:
24
4
2022
medline:
27
4
2022
entrez:
23
4
2022
Statut:
ppublish
Résumé
24S-hydroxycholesterol (i.e., cerebrosterol, 24S-OH-Chol) is the main form of cholesterol elimination from the brain. Liquid chromatography-tandem mass spectrometry methods were developed for the quantification of the total and unesterified/unbound fractions of 24S-OH-Chol, its monosulfate, monoglucuronide, and diconjugate derivatives (24S-OH-Chol-3sulfate [3S], 24S-OH-Chol-24glucuronide [24G] and 24S-OH-Chol-3S, 24G, respectively) in human plasma. Linearity, precision, accuracy, and extraction recovery were validated within the typical physiological and pathological ranges of concentrations for each compound. The lower limit of quantifications was 2.00, 0.33, 0.26, and 0.74 ng/ml for 24S-OH-Chol, 24S-OH-Chol-24G, 24S-OH-Chol-3S, and 24-OH-Chol-3S, 24G, respectively. Extraction recovery values in total and unbound plasma fractions were also analyzed in murine and monkey plasma and varied from 73% in mouse to 113% in cynomolgus monkey. The methods could rapidly (less than 7 min) quantify individual compounds with high sensitivity, accuracy (bias ≤15%), and reproducibility (coefficient of variation [CV] ≤ 17%). Their clinical applications were validated by measuring levels of the 4 compounds in samples from 20 noncholestatic donors, 5 cholestatic patients suffering from primary biliary cirrhosis, and 10 patients suffering from biliary stenosis. Results highlight the abundance of 24S-OH-Chol in the total fraction and the abundance of 24S-OH-Chol-3S and 24G in the unbound ones. While the latter strongly accumulate in plasma fractions of cholestatic patients, levels of 24S-OH-Chol remained similar to those of healthy donors. Our results indicate that this approach is suitable for monitoring cerebrosterol and its conjugates in large-scale clinical studies.
Substances chimiques
Glucuronides
0
Hydroxycholesterols
0
Sulfates
0
24-hydroxycholesterol
47IMW63S3F
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e4827Subventions
Organisme : Canadian Foundation for Innovation
ID : 17745
Organisme : CIHR
ID : PJT148611
Pays : Canada
Informations de copyright
© 2022 John Wiley & Sons, Ltd.
Références
Björkhem I, Lütjohann D, Diczfalusy U, Ståhle L, Ahlborg G, Wahren J. Cholesterol homeostasis in human brain: Turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J Lipid Res. 1998;39(8):1594-1600.
Pitas RE, Boyles JK, Lee SH, Foss D, Mahley RW. Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins. Biochim Biophys Acta. 1987;917:148-161.
Björkhem I. Crossing the barrier: Oxysterols as cholesterol transporters and metabolic modulators in the brain. J Intern Med. 2006;260:493-508.
Russell DW. Oxysterol biosynthetic enzymes. Biochim Biophys Acta. 2000;1(529):126-135.
Björkhem I, Heverin M, Leoni V, Meaney S, Diczfalusy U. Oxysterols and Alzheimer's disease. Acta Neurol Scand Suppl. 2006;185:43-49.
Leoni V, Masterman T, Mousavi F, et al. Diagnostic use of cerebral and extracerebral oxysterols. Clin Chem Lab Med. 2004;42:186-191.
Kölsch H, Heun R, Kerksiek A, Bergmann K, Maier W, Lütjohann D. Altered levels of plasma 24S- and 27-hydroxycholesterol in demented patients. Neurosci Lett. 2004;368:303-308.
Leoni V, Mariotti C, Tabrizi S, et al. Plasma 24S-hydroxycholesterol and caudate MRI in pre-manifest and early Huntington's disease. Brain. 2008;131:2851-2859.
Dzeletovic S, Breuer O, Lund E, Diczfalusy U. Determination of cholesterol oxidation products in human plasma by isotope dilution-mass spectrometry. Anal Biochem. 1995;225:73-80.
Griffiths WJ, Abdel-Khalik J, Crick PJ, Yutuc E, Wang Y. New methods for analysis of oxysterols and related compounds by LC-MS. J Steroid Biochem Mol Biol. 2016;162:4-26.
Burkard I, von Eckardstein A, Waeber G, Vollenweider P, Rentsch K. Lipoprotein distribution and biological variation of 24S- and 27-hydroxycholesterol in healthy volunteers. Atherosclerosis. 2007;194:71-78.
Babiker A, Diczfalusy U. Transport of side-chain oxidized oxysterols in the human circulation. Biochim Biophys Acta. 1998;1(392):333-339.
Bjorkhem I, Andersson U, Ellis E, et al. From brain to bile. Evidence that conjugation and omega-hydroxylation are important for elimination of 24S-hydroxycholesterol (cerebrosterol) in humans. J Biol Chem. 2001;276:37004-37010.
Kumar B, Chung B, Lee Y-J, Yi H, Lee B-H, Jung B. Gas chromatography-mass spectrometry-based simultaneous quantitative analytical method for urinary oxysterols and bile acids in rats. Anal Biochem. 2011;408:242-252.
Li-Hawkins J, Lund E, Bronson A, Russell D. Expression cloning of an oxysterol 7alpha-hydroxylase selective for 24-hydroxycholesterol. J Biol Chem. 2000;275:16543-16549.
Norlin M, Toll A, Björkhem I, Wikvall K. 24-hydroxycholesterol is a substrate for hepatic cholesterol 7alpha-hydroxylase (CYP7A). J Lipid Res. 2000;41:1629-1639.
Guillemette C. Pharmacogenomics of human UDP-glucuronosyltransferase enzymes. Pharmacogenomics J. 2003;3:136-158.
Falany C. Enzymology of human cytosolic sulfotransferases. FASEB J. 1997;11:206-216.
Gamage N, Barnett A, Hempel N, et al. Human sulfotransferases and their role in chemical metabolism. Toxicol Sci. 2006;90:5-22.
Cook IT, Duniec-Dmuchowski Z, Kocarek TA, Runge-Morris M, Falany CN. 24-hydroxycholesterol sulfation by human cytosolic sulfotransferases: Formation of monosulfates and disulfates, molecular modeling, sulfatase sensitivity, and inhibition of liver x receptor activation. Drug Metab Dispo. 2009;37:2069-2078.
Meng L, Griffiths W, Nazer H, Yang Y, Sjövall J. High levels of (24S)-24-hydroxycholesterol 3-sulfate, 24-glucuronide in the serum and urine of children with severe cholestatic liver disease. J Lipid Res. 1997;38:926-934.
Acimovic J, Lovgren-Sandblom A, Olin M, et al. Sulphatation does not appear to be a protective mechanism to prevent oxysterol accumulation in humans and mice. PLoS One. 2013;8:e68031. https://doi.org/10.1371/journal.pone.0068031
Trottier J, Caron P, Straka RJ, Barbier O. Profile of serum bile acids in noncholestatic volunteers: Gender-related differences in response to fenofibrate. Clin Pharmacol Ther. 2011;90:279-286.
Trottier J, Bialek A, Caron P, Straka RJ, Milkiewicz P, Barbier O. Profiling circulating and urinary bile acids in patients with biliary obstruction before and after biliary stenting. PLoS One. 2011;6:e22094. https://doi.org/10.1371/journal.pone.0022094
Gregoire L, Smith T, Senanayake V, et al. Plasmalogen precursor analog treatment reduces levodopa-induced dyskinesias in parkinsonian monkeys. Behav Brain Res. 2015;286:328-337.
Caron P, Trottier J, Verreault M, Belanger J, Kaeding J, Barbier O. Enzymatic production of bile Acid glucuronides used as analytical standards for liquid chromatography-mass spectrometry analyses. Mol Pharm. 2006;3:293-302.
Burkard I, Rentsch KM, von Eckardstein A. Determination of 24S- and 27-hydroxycholesterol in plasma by high-performance liquid chromatography-mass spectrometry. J Lipid Res. 2004;45:776-781.
Mendiara I, Domeno C, Nerin C. Development of a fast sample treatment for the analysis of free and bonded sterols in human serum by LC-MS. J Sep Sci. 2012;35:3308-3316.
DeBarber AE, Lutjohann D, Merkens L, Steiner RD. Liquid chromatography-tandem mass spectrometry determination of plasma 24S-hydroxycholesterol with chromatographic separation of 25-hydroxycholesterol. Anal Biochem. 2008;381:151-153.
Griffiths WJ, Crick PJ, Wang Y. Methods for oxysterol analysis: Past, present and future. Biochem Pharmacol. 2013;86:3-14.
Lutjohann D, Breuer O, Ahlborg G, et al. Cholesterol homeostasis in human brain: Evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation. Proc Natl Acad Sci U S A. 1996;93:9799-9804.
Matysik S, Schmitz G. Application of gas chromatography-triple quadrupole mass spectrometry to the determination of sterol components in biological samples in consideration of the ionization mode. Biochimie. 2013;95:489-495.
Bandaru VV, Haughey NJ. Quantitative detection of free 24S-hydroxycholesterol, and 27-hydroxycholesterol from human serum. BMC Neurosci. 2014;15:137. https://doi.org/10.1186/s12868-014-0137-z
Quehenberger O, Armando AM, Brown AH, et al. Lipidomics reveals a remarkable diversity of lipids in human plasma. J Lipid Res. 2010;51:3299-3305.
Pares A. Old and novel therapies for primary biliary cirrhosis. Semin Liver Dis. 2014;34:341-351.