title: Accurate quantification of sphingosine-1-phosphate in normal and Fabry disease plasma, cells and tissues by LC-MS/MS with (13)C-encoded natural S1P as internal standard.
abstract: We developed a mass spectrometric procedure to quantify sphingosine-1-phosphate (S1P) in biological materials. The use of newly synthesized (13)C5 C18-S1P and commercial C17-S1P as internal standards rendered very similar results with respect to linearity, limit of detection and limit of quantitation. Caution is warranted with determination of plasma S1P levels. Earlier it was reported that S1P is elevated in plasma of Fabry disease patients. We investigated this with the improved quantification. No clear conclusion could be drawn for patient plasma samples given the lack of uniformity of blood collection and plasma preparation. To still obtain insight, plasma and tissues were identically collected from α-galactosidase A deficient Fabry mice and matched control animals. No significant difference was observed in plasma S1P levels. A significant 2.3 fold increase was observed in kidney of Fabry mice, but not in liver and heart. Comparative analysis of S1P in cultured fibroblasts from normal subjects and classically affected Fabry disease males revealed no significant difference. In conclusion, accurate quantification of S1P in biological materials is feasible by mass spectrometry using the internal standards (13)C5 C18-S1P or C17-S1P. Significant local increases of S1P in the kidney might occur in Fabry disease as suggested by the mouse model.
authors.affiliation: Department of Medical Biochemistry, Leiden Institute of Chemistry, Leiden University, The Netherlands.
authors.forename: Mina
authors.initials: M
authors.lastname: Mirzaian
authors.affiliation: Department of Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University, The Netherlands.
authors.forename: Patrick
authors.initials: P
authors.lastname: Wisse
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ferraz
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: André R A
authors.initials: ARA
authors.lastname: Marques
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Tanit L
authors.initials: TL
authors.lastname: Gabriel
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Cindy P A A
authors.initials: CPAA
authors.lastname: van Roomen
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Roelof
authors.initials: R
authors.lastname: Ottenhoff
authors.affiliation: Department of Medical Biochemistry, Leiden Institute of Chemistry, Leiden University, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: van Eijk
authors.affiliation: Department of Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University, The Netherlands.
authors.forename: Jeroen D C
authors.initials: JDC
authors.lastname: Codée
authors.affiliation: Department of Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University, The Netherlands.
authors.forename: Gijsbert A
authors.initials: GA
authors.lastname: van der Marel
authors.affiliation: Department of Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University, The Netherlands.
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
authors.affiliation: Department of Medical Biochemistry, Leiden Institute of Chemistry, Leiden University, The Netherlands. Electronic address: j.m.f.g.aerts@lic.leidenuniv.nl.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Aerts
mesh_terms: D000818:Animals; D002247:Carbon Isotopes; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D000795:Fabry Disease / Q000097:blood* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D008246:Lysophospholipids / Q000097:blood*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012015:Reference Standards; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood; D053719:Tandem Mass Spectrometry / Q000592:standards*
chemical_list: D002247:Carbon Isotopes; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: Fabry disease; Mass spectrometry; Quantification; Sphingolipid; Sphingosine-1-phosphate