title: Tandem Mass Spectrometry Quantitation of Lyso-Gb3 and Six Related Analogs in Plasma for Fabry Disease Patients.
abstract: 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.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Boutin
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Pamela
authors.initials: P
authors.lastname: Lavoie
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Mona
authors.initials: M
authors.lastname: Abaoui
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Christiane
authors.initials: C
authors.lastname: Auray-Blais
mesh_terms: D002851:Chromatography, High Pressure Liquid; D000795:Fabry Disease / Q000097:blood*; D006017:Glycolipids / Q000097:blood* / Q000737:chemistry*; D006801:Humans; D057230:Limit of Detection; D008297:Male; D012015:Reference Standards; D052616:Solid Phase Extraction; D013107:Sphingolipids / Q000097:blood* / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: D006017:Glycolipids; D013107:Sphingolipids; C063288:globotriaosyl lysosphingolipid
keywords: Fabry disease; Lyso-Gb3; MS/MS; analogs; biomarkers; plasma; tandem mass spectrometry; ultra-performance liquid chromatography (UPLC)