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A validated LC-MS/MS assay for quantification of 24(S)-hydroxycholesterol in plasma and cerebrospinal fluid.
Sidhu, Rohini; Jiang, Hui; Farhat, Nicole Y; Carrillo-Carrasco, Nuria; Woolery, Myra; Ottinger, Elizabeth; Porter, Forbes D; Schaffer, Jean E; Ory, Daniel S; Jiang, Xuntian.
Afiliación
  • Sidhu R; Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO 63110.
  • Jiang H; Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO 63110.
  • Farhat NY; Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
  • Carrillo-Carrasco N; Therapeutics for Rare and Neglected Diseases National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850.
  • Woolery M; Nursing Department, National Institutes of Health, Bethesda, MD 20892.
  • Ottinger E; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850.
  • Porter FD; Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
  • Schaffer JE; Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO 63110.
  • Ory DS; Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO 63110.
  • Jiang X; Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO 63110.
J Lipid Res ; 56(6): 1222-33, 2015 Jun.
Article en En | MEDLINE | ID: mdl-25866316
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-ß-cyclodextrin (HP-ß-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-ß-CD in Niemann-Pick type C1 patients, in which 24(S)-HC is used as a pharmacodynamic biomarker.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatografía Liquida / Enfermedad de Niemann-Pick Tipo C / Espectrometría de Masas en Tándem / Hidroxicolesteroles Límite: Humans País/Región como asunto: America do norte Idioma: En Revista: J Lipid Res Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatografía Liquida / Enfermedad de Niemann-Pick Tipo C / Espectrometría de Masas en Tándem / Hidroxicolesteroles Límite: Humans País/Región como asunto: America do norte Idioma: En Revista: J Lipid Res Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos