title: Complexity and pitfalls of mass spectrometry-based targeted metabolomics in brain research.
abstract: Current quantitative metabolomic research in brain tissue is challenged by several analytical issues. To compare data of metabolite pattern, ratios of individual metabolite concentrations and composed classifiers characterizing a distinct state, standardized workup conditions, and extraction medium are crucial. Differences in physicochemical properties of individual compounds and compound classes such as polarity determine extraction yields and, thus, ratios of compounds with varying properties. Also, variations in suppressive effects related to coextracted matrix components affect standards or references and their concentration-dependent responses.The selection of a common tissue extraction protocol is an ill-posed problem because it can be regarded as a multiple objective decision depending on factors such as sample handling practicability, measurement precision, control of matrix effects, and relevance of the chemical assay. This study systematically evaluates the impact of extraction solvents and the impact of the complex brain tissue on measured metabolite levels, taking into account ionization efficiency as well as challenges encountered in the trace-level quantification of the analytes in brain matrices. In comparison with previous studies that relied on nontargeted platforms, consequently emphasizing the global behavior of the metabolomic fingerprint, here we focus on several series of metabolites spanning over extensive polarity, concentration, and molecular mass ranges.
authors.affiliation: BIOCRATES Life Sciences, 6020 Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Urban
authors.forename: David P
authors.initials: DP
authors.lastname: Enot
authors.forename: Guido
authors.initials: G
authors.lastname: Dallmann
authors.forename: Lisa
authors.initials: L
authors.lastname: Körner
authors.forename: Verena
authors.initials: V
authors.lastname: Forcher
authors.forename: Peter
authors.initials: P
authors.lastname: Enoh
authors.forename: Therese
authors.initials: T
authors.lastname: Koal
authors.forename: Matthias
authors.initials: M
authors.lastname: Keller
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Deigner
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D035843:Biomedical Research; D001921:Brain / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods*; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D012997:Solvents; D034421:Sus scrofa
chemical_list: D012997:Solvents