title: Ultra performance liquid chromatography - mass spectrometry studies of formalin-induced alterations of human brain lipidome.
abstract: The development of 'omics' sciences offers new opportunities for the study of neurodegenerative diseases but increases at the same time the sample demand on brain banks that collect and store valuable human post-mortem tissue. Our study aims to evaluate in lipidomics the potential of formalin-fixed tissue compared with the cryopreservation method, considered as the gold standard for biochemical research. Two complementary liquid chromatography/mass spectrometry analytical platforms were used on the basis of hybrid quadrupole time-of-flight and triple quadrupole mass spectrometers. Untargeted fingerprinting, semitargeted profiling of specific lipid classes and targeted monitoring of lipid species were performed in formalin-fixed and cryopreserved samples to provide detailed information at the molecular level on the formalin-induced alterations of the brain tissue. In vitro incubations of lipid standards were also performed to further describe the degradation processes induced by formaldehyde. Phospholipid compounds were found to be extensively hydrolysed, whilst the sphingolipid ones were preserved. N-methylation and N-formylation of amine-containing phospholipids have also been evidenced. These findings show that the potential detrimental effect of formalin on the analytes of interest must be taken into account when analysing formalin-fixed samples.
authors.affiliation: Chimie-Toxicologie Analytique et Cellulaire, UMR CNRS 8638 COMETE, Faculté des Sciences Pharmaceutiques et Biologiques de Paris, Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France; Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, 91198, Gif-sur-Yvette, France; Technologie Servier, 45000, Orléans, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Gaudin
authors.forename: Maï
authors.initials: M
authors.lastname: Panchal
authors.forename: Sophie
authors.initials: S
authors.lastname: Ayciriex
authors.forename: Erwan
authors.initials: E
authors.lastname: Werner
authors.forename: Alain
authors.initials: A
authors.lastname: Brunelle
authors.forename: David
authors.initials: D
authors.lastname: Touboul
authors.forename: Claire
authors.initials: C
authors.lastname: Boursier-Neyret
authors.forename: Nicolas
authors.initials: N
authors.lastname: Auzeil
authors.forename: Bernard
authors.initials: B
authors.lastname: Walther
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.forename: Olivier
authors.initials: O
authors.lastname: Laprévote
mesh_terms: D001923:Brain Chemistry / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015925:Cryopreservation; D005557:Formaldehyde / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000032:analysis*; D013058:Mass Spectrometry / Q000379:methods*; D025341:Principal Component Analysis; D016707:Tissue Fixation
chemical_list: D008055:Lipids; D005557:Formaldehyde
keywords: formalin fixation; lipidomics; lipids; phospholipids; sphingolipids