A sensitive and specific LC-MS/MS method for rapid diagnosis of Niemann-Pick C1 disease from human plasma

Autor: Jessie Zhang, Hideji Fujiwara, Frances M. Platt, Jean E. Schaffer, Danielle Taylor te Vruchte, Daniel S. Ory, Anneliese O. Speak, Dennis J. Dietzen, Rohini Sidhu, Forbes D. Porter, David E. Scherrer, Nicole M. Yanjanin, Xuntian Jiang
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Adult
Male
Time Factors
Adolescent
Oxysterol
QD415-436
Pharmacology
Tandem mass spectrometry
Sensitivity and Specificity
Biochemistry
diagnostic tools
Dimethylglycine
Young Adult
chemistry.chemical_compound
Endocrinology
Tandem Mass Spectrometry
Liquid chromatography–mass spectrometry
hemic and lymphatic diseases
Methods
medicine
Humans
Child
Derivatization
Ketocholesterols
Chromatography
High Pressure Liquid
Niemann–Pick disease
type C
Chromatography
Infant
Newborn
neurodegeneration
Infant
cholesterol
Niemann-Pick Disease
Type C
Sarcosine
Cell Biology
Middle Aged
medicine.disease
chemistry
Case-Control Studies
Child
Preschool
Calibration
oxysterols
Female
lipids (amino acids
peptides
and proteins)
NPC1
Niemann–Pick disease
liquid chromatography/tandem mass spectrometry
Niemann-Pick disease
Cholestanols
Zdroj: Journal of Lipid Research, Vol 52, Iss 7, Pp 1435-1445 (2011)
ISSN: 1539-7262
0022-2275
Popis: Niemann-Pick type C1 (NPC1) disease is a rare, progressively fatal neurodegenerative disease for which there are no FDA-approved therapies. A major barrier to developing new therapies for this disorder has been the lack of a sensitive and noninvasive diagnostic test. Recently, we demonstrated that two cholesterol oxidation products, specifically cholestane-3β,5α,6β-triol (3β,5α,6β-triol) and 7-ketocholesterol (7-KC), were markedly increased in the plasma of human NPC1 subjects, suggesting a role for these oxysterols in diagnosis of NPC1 disease and evaluation of therapeutics in clinical trials. In the present study, we describe the development of a sensitive and specific LC-MS/MS method for quantifying 3β,5α,6β-triol and 7-KC human plasma after derivatization with N,N-dimethylglycine. We show that dimethylglycine derivatization successfully enhanced the ionization and fragmentation of 3β,5α,6β-triol and 7-KC for mass spectrometric detection of the oxysterol species in human plasma. The oxysterol dimethylglycinates were resolved with high sensitivity and selectivity, and enabled accurate quantification of 3β,5α,6β-triol and 7-KC concentrations in human plasma. The LC-MS/MS assay was able to discriminate with high sensitivity and specificity between control and NPC1 subjects, and offers for the first time a noninvasive, rapid, and highly sensitive method for diagnosis of NPC1 disease.
Databáze: OpenAIRE
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