title: HPLC-ESI-MS/MS of brain neurotransmitter modulator lobeline and related piperidine alkaloids in Lobelia inflata L.
abstract: There is a renewed interest in lobelia alkaloids because of their activity on the central nervous system. Lobeline, the most active of them, a nicotinic receptor ligand and neurotransmitter transporter inhibitor, is a candidate pharmacotherapy for metamphetamine abuse. In the present work, high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry in positive ion mode was used for investigating the alkaloid profile in Lobelia inflata L. Chromatographic separations were achieved on a Gemini C6-phenyl reversed-phase column providing good peak shape and improved selectivity. Being mostly 2,6-disubstituted piperidines, lobelia alkaloids presented abundant [M + H](+) ions with typical fragmentation. Identification was possible from a few specific ions, especially those resulting from excision of one of the substituents. Based on fragmentation pattern of lobeline as reference compound, 52 alkaloids were identified in the aqueous methanolic extract of L. inflata in contrast to the previously known some 20. Structural variability of these alkaloids identified arises basically from their substituents which can be phenyl-2-ketoethyl- or phenyl-2-hydroxyethyl units as well as their methyl-, ethyl- or propyl- homologues attached in different combinations. Several propyl homologue lobelia alkaloids and five hydroxypiperidine derivatives were found in the plant at the first time. In addition to 8-O-esters of 2-monosubstituted piperidine alkaloids previously reported by us in L. inflata, a 3-hydroxy-3-phenylpropanoic acid ester of hydroxyallosedamine ring-substituted was also identified as a new natural product. High-performance liquid chromatography-electrospray ionization tandem mass spectrometry can be successfully applied to Lobeliacae plant samples in the routine screening for new and known bioactive constituents, quality control of the crude drug, lobelia herba, alkaloid production studies, breeding and chemotaxonomy.
authors.affiliation: Department of Pharmacognosy, Semmelweis University, Üllői út 26, H-1085, Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Kursinszki
authors.affiliation: Department of Pharmacognosy, Semmelweis University, Üllői út 26, H-1085, Budapest, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Szőke
mesh_terms: D000470:Alkaloids / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D029746:Lobelia / Q000737:chemistry*; D008120:Lobeline / Q000032:analysis*; D018377:Neurotransmitter Agents / Q000032:analysis*; D010880:Piperidines / Q000032:analysis; D010936:Plant Extracts / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000470:Alkaloids; D018377:Neurotransmitter Agents; D010880:Piperidines; D010936:Plant Extracts; D008120:Lobeline
keywords: HPLC-ESI-MS/MS; Lobelia inflata; lobeline; piperidine alkaloids; tandem mass spectrometry