Tandem Mass Spectrometry Quantitation of Lyso-Gb3 and Six Related Analogs in Plasma for Fabry Disease Patients.
Fabry disease is an X-linked lysosomal storage disorder, caused by a deficit in α-galactosidase A enzyme activity, leading to the storage of sphingolipids such as globotriaosylsphingosine (lyso-Gb3 ), globotriaosylceramide (Gb3 ), and galabiosylceramide (Ga2 ) in organs, tissues and biological fluids. A recent metabolomic study performed in plasma revealed lyso-Gb3 analogs as novel Fabry disease biomarkers. These molecules correspond to lyso-Gb3 with different chemical modifications on the sphingosine chain (-C2 H4 , -H2 , +O, +H2 O, +H2 O2, and +H2 O3 ). An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the multiplex analysis of lyso-Gb3 and its 6 analogs in plasma. The samples are prepared by solid phase extraction using mixed-mode strong cation exchange (MCX) cartridges. An in-house synthesized N-glycinated lyso-Gb3 derivative was used for the internal standard. The limits of detection (LODs) measured for lyso-Gb3 and its analogs ranged from 0.06 to 0.29 nM. © 2016 by John Wiley & Sons, Inc.
['Boutin|Michel|M|', 'Lavoie|Pamela|P|', 'Abaoui|Mona|M|', 'Auray-Blais|Christiane|C|']
D002851:Chromatography, High Pressure Liquid D000795:Fabry Disease D006017:Glycolipids D006801:Humans D057230:Limit of Detection D008297:Male D012015:Reference Standards D052616:Solid Phase Extraction D013107:Sphingolipids D053719:Tandem Mass Spectrometry
tandem mass spectrometry Lyso-Gb3 analogs plasma Fabry disease biomarkers MS/MS ultra-performance liquid chromatography (UPLC)