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

Yutuc E., Dickson A. L., Pacciarini M., Griffiths L., Baker P. R. S., Connell L., ...Daha Fazla

ANALYTICA CHIMICA ACTA, cilt.1154, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1154
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.aca.2021.338259
  • Dergi Adı: ANALYTICA CHIMICA ACTA
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), Artic & Antarctic Regions, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, Communication Abstracts, Compendex, EMBASE, Food Science & Technology Abstracts, MEDLINE, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Anahtar Kelimeler: Cholesterol, Hydroxycholesterol, Cholestenoic acid, Bile acid, LC-MS, Derivatisation, Isotope-labelled standard, BILE-ACIDS, PARKINSONS-DISEASE, ACOX2 DEFICIENCY, LIPIDOMICS, 24S-HYDROXYCHOLESTEROL, BIOMARKERS, PRODUCTS, STEROLS, ENZYMES, LIPIDS
  • Gazi Üniversitesi Adresli: Evet

Özet

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. (C) 2021 The Authors. Published by Elsevier B.V.