A new simple and rapid LC-ESI-MS/MS method for quantification of plasma oxysterols as dimethylaminobutyrate esters. Its successful use for the diagnosis of Niemann-Pick type C disease

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Abstract

Two oxysterols, cholestan-3β,5α,6β-triol (C-triol) and 7-ketocholesterol (7-KC), have been recently proposed as diagnostic markers of Niemann-Pick type C (NP-C) disease, representing a potential alternative diagnostic tool to the more invasive and time consuming filipin test in cultured fibroblasts. Usually, the oxysterols are detected and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using atmospheric pressure chemical ionization (APCI) or electro-spray-ionization (ESI) sources, after a variety of derivatization procedures to enhance sensitivity. We developed a sensitive LC-MS/MS method to quantify the oxysterols in plasma as dimethylaminobutyrate ester, suitable for ESI analysis. This method, with an easy liquid-phase extraction and a short derivatization procedure, has been validated to demonstrate specificity, linearity, recovery, lowest limit of quantification, accuracy and precision. The assay was linear over a concentration range of 0.5-200. ng/mL for C-triol and 1.0-200. ng/mL for 7-KC. Intra-day and inter-day coefficients of variation (CV%) were

Original languageEnglish
Pages (from-to)93-100
Number of pages8
JournalClinica Chimica Acta
Volume437
DOIs
Publication statusPublished - Nov 1 2014

Fingerprint

Type C Niemann-Pick Disease
Ionization
Esters
Filipin
Plasmas
Liquid chromatography
Ion sources
Fibroblasts
Atmospheric pressure
Mass spectrometry
Assays
Recovery
Liquids
Liquid-Liquid Extraction
Atmospheric Pressure
Tandem Mass Spectrometry
Liquid Chromatography
7-ketocholesterol
Oxysterols

Keywords

  • Dimethylaminobutyrate ester derivative
  • Electrospray ionization analysis
  • Liquid chromatography-tandem-mass spectrometry
  • Niemann-Pick C disease
  • Oxysterols

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical
  • Medicine(all)

Cite this

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title = "A new simple and rapid LC-ESI-MS/MS method for quantification of plasma oxysterols as dimethylaminobutyrate esters. Its successful use for the diagnosis of Niemann-Pick type C disease",
abstract = "Two oxysterols, cholestan-3β,5α,6β-triol (C-triol) and 7-ketocholesterol (7-KC), have been recently proposed as diagnostic markers of Niemann-Pick type C (NP-C) disease, representing a potential alternative diagnostic tool to the more invasive and time consuming filipin test in cultured fibroblasts. Usually, the oxysterols are detected and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using atmospheric pressure chemical ionization (APCI) or electro-spray-ionization (ESI) sources, after a variety of derivatization procedures to enhance sensitivity. We developed a sensitive LC-MS/MS method to quantify the oxysterols in plasma as dimethylaminobutyrate ester, suitable for ESI analysis. This method, with an easy liquid-phase extraction and a short derivatization procedure, has been validated to demonstrate specificity, linearity, recovery, lowest limit of quantification, accuracy and precision. The assay was linear over a concentration range of 0.5-200. ng/mL for C-triol and 1.0-200. ng/mL for 7-KC. Intra-day and inter-day coefficients of variation (CV{\%}) were",
keywords = "Dimethylaminobutyrate ester derivative, Electrospray ionization analysis, Liquid chromatography-tandem-mass spectrometry, Niemann-Pick C disease, Oxysterols",
author = "Sara Boenzi and Federica Deodato and Roberta Taurisano and Diego Martinelli and Daniela Verrigni and Rosalba Carrozzo and Enrico Bertini and Anna Pastore and Carlo Dionisi-Vici and Johnson, {David W.}",
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T1 - A new simple and rapid LC-ESI-MS/MS method for quantification of plasma oxysterols as dimethylaminobutyrate esters. Its successful use for the diagnosis of Niemann-Pick type C disease

AU - Boenzi, Sara

AU - Deodato, Federica

AU - Taurisano, Roberta

AU - Martinelli, Diego

AU - Verrigni, Daniela

AU - Carrozzo, Rosalba

AU - Bertini, Enrico

AU - Pastore, Anna

AU - Dionisi-Vici, Carlo

AU - Johnson, David W.

PY - 2014/11/1

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N2 - Two oxysterols, cholestan-3β,5α,6β-triol (C-triol) and 7-ketocholesterol (7-KC), have been recently proposed as diagnostic markers of Niemann-Pick type C (NP-C) disease, representing a potential alternative diagnostic tool to the more invasive and time consuming filipin test in cultured fibroblasts. Usually, the oxysterols are detected and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using atmospheric pressure chemical ionization (APCI) or electro-spray-ionization (ESI) sources, after a variety of derivatization procedures to enhance sensitivity. We developed a sensitive LC-MS/MS method to quantify the oxysterols in plasma as dimethylaminobutyrate ester, suitable for ESI analysis. This method, with an easy liquid-phase extraction and a short derivatization procedure, has been validated to demonstrate specificity, linearity, recovery, lowest limit of quantification, accuracy and precision. The assay was linear over a concentration range of 0.5-200. ng/mL for C-triol and 1.0-200. ng/mL for 7-KC. Intra-day and inter-day coefficients of variation (CV%) were

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KW - Niemann-Pick C disease

KW - Oxysterols

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