title: Pyrylium Salts as Reactive Matrices for MALDI-MS Imaging of Biologically Active Primary Amines.
abstract: Many neuroactive substances, including endogenous biomolecules, environmental compounds, and pharmaceuticals possess primary amine functional groups. Among these are catecholamine neurotransmitters (e.g., dopamine), many substituted phenethylamines (e.g., amphetamine), as well as amino acids and neuropeptides. In most cases, mass spectrometric (ESI and MALDI) analyses of trace amounts of such compounds are challenging because of their poor ionization properties. We present a method for chemical derivatization of primary amines by reaction with pyrylium salts that facilitates their detection by MALDI-MS and enables the imaging of primary amines in brain tissue sections. A screen of pyrylium salts revealed that the 2,4-diphenyl-pyranylium ion efficiently derivatizes primary amines and can be used as a reactive MALDI-MS matrix that induces both derivatization and desorption. MALDI-MS imaging with such matrix was used to map the localization of dopamine and amphetamine in brain tissue sections and to quantitatively map the distribution of the neurotoxin β-N-methylamino-L-alanine.
authors.affiliation: Biomolecular Imaging and Proteomics, National Center for Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591 BMC, 75124, Uppsala, Sweden.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Shariatgorji
authors.forename: Anna
authors.initials: A
authors.lastname: Nilsson
authors.forename: Patrik
authors.initials: P
authors.lastname: Källback
authors.forename: Oskar
authors.initials: O
authors.lastname: Karlsson
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Zhang
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsson
authors.forename: Per E
authors.initials: PE
authors.lastname: Andren
mesh_terms: D000588:Amines / Q000032:analysis*; D000599:Amino Acids, Diamino / Q000032:analysis; D000661:Amphetamine / Q000032:analysis; D000818:Animals; D001923:Brain Chemistry; D000697:Central Nervous System Stimulants / Q000032:analysis; D000087522:Cyanobacteria Toxins; D004298:Dopamine / Q000032:analysis; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry*; D008297:Male; D008810:Mice, Inbred C57BL; D017208:Rats, Wistar; D012492:Salts / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D000588:Amines; D000599:Amino Acids, Diamino; D000697:Central Nervous System Stimulants; D000087522:Cyanobacteria Toxins; D006575:Heterocyclic Compounds, 3-Ring; D012492:Salts; C505939:pyrylium 1; C001824:beta-N-methylamino-L-alanine; D000661:Amphetamine; D004298:Dopamine
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18126-31
references.pmid: 18776051
references.citation: Anal Chem. 2010 Nov 1;82(21):8800-6
references.pmid: 20939518
references.citation: J Mass Spectrom. 2003 Jul;38(7):699-708
references.pmid: 12898649
references.citation: Analyst. 2012 Dec 21;137(24):5757-62
references.pmid: 23087915
references.citation: Anal Chem. 2011 Jan 1;83(1):2-7
references.pmid: 21049956
references.citation: Mass Spectrom Rev. 2011 Jan-Feb;30(1):101-20
references.pmid: 20169623
references.citation: Carbohydr Res. 2012 May 1;352:94-100
references.pmid: 22425443
references.citation: Anal Chem. 2012 Nov 6;84(21):8996-9001
references.pmid: 23009618
references.citation: Neuropharmacology. 2008 Jun;54(7):1143-52
references.pmid: 18423776
references.citation: Anal Chem. 2012 May 15;84(10):4603-7
references.pmid: 22507246
references.citation: Neuron. 2014 Nov 19;84(4):697-707
references.pmid: 25453841
references.citation: Nat Protoc. 2008;3(8):1341-9
references.pmid: 18714302
references.citation: Proteomics. 2014 Apr;14(7-8):810-9
references.pmid: 23818158
references.citation: J Mass Spectrom. 2011 Aug;46(8):840-6
references.pmid: 21834023
references.citation: Anal Chem. 2014 Oct 21;86(20):10030-5
references.pmid: 25331774
references.citation: J Am Soc Mass Spectrom. 2004 Dec;15(12):1833-7
references.pmid: 15589759
references.citation: Anal Chem. 2012 Dec 4;84(23):10291-7
references.pmid: 23113720
references.citation: J Am Chem Soc. 1971 Jul 14;93(14):3530-2
references.pmid: 5560474
references.citation: Toxicol Sci. 2012 Dec;130(2):391-404
references.pmid: 22872059
references.citation: Nat Methods. 2007 Oct;4(10):828-33
references.pmid: 17901873
references.citation: Nature. 1999 May 20;399(6733):243-6
references.pmid: 10353246
references.citation: Rapid Commun Mass Spectrom. 2012 Aug 30;26(16):1849-58
references.pmid: 22777787
references.citation: Talanta. 2013 Oct 15;115:442-50
references.pmid: 24054616
references.citation: Analyst. 2014 Nov 21;139(22):5999-6009
references.pmid: 25268849
references.citation: Neuropsychopharmacology. 2014 Jan;39(1):34-49
references.pmid: 23966069
references.citation: PLoS One. 2012;7(12):e52322
references.pmid: 23300642
references.citation: J Mass Spectrom. 2014 Aug;49(8):665-73
references.pmid: 25044893
references.citation: Mass Spectrom Rev. 2015 Nov-Dec;34(6):627-40
references.pmid: 24916100
references.citation: Methods Mol Biol. 2012;800:227-40
references.pmid: 21964792
references.citation: Anal Chem. 2013 Dec 3;85(23):11576-84
references.pmid: 24134553