title: Quality markers addressing preanalytical variations of blood and plasma processing identified by broad and targeted metabolite profiling.
abstract: BACKGROUND
  Metabolomics is a valuable tool with applications in almost all life science areas. There is an increasing awareness of the essential need for high-quality biospecimens in studies applying omics technologies and biomarker research. Tools to detect effects of both blood and plasma processing are a key for assuring reproducible and credible results. We report on the response of the human plasma metabolome to common preanalytical variations in a comprehensive metabolomics analysis to reveal such high-quality markers.
  
  
  METHODS
  Human EDTA blood was subjected to preanalytical variations while being processed to plasma: microclotting, prolonged processing times at different temperatures, hemolysis, and contamination with buffy layer. In a second experiment, EDTA plasma was incubated at different temperatures for up to 16 h. Samples were subjected to GC-MS and liquid chromatography-tandem mass spectrometry-based metabolite profiling (MxP™ Broad Profiling) complemented by targeted methods, i.e., sphingoids (as part of MxP™ Lipids), MxP™ Catecholamines, and MxP™ Eicosanoids.
  
  
  RESULTS
  Short-term storage of blood, hemolysis, and short-term storage of noncooled plasma resulted in statistically significant increases of 4% to 19% and decreases of 8% to 12% of the metabolites. Microclotting, contamination of plasma with buffy layer, and short-term storage of cooled plasma were of less impact on the metabolome (0% to 11% of metabolites increased, 0% to 8% decreased).
  
  
  CONCLUSIONS
  The response of the human plasma metabolome to preanalytical variation demands implementation of thorough quality assurance and QC measures to obtain reproducible and credible results from metabolomics studies. Metabolites identified as sensitive to preanalytics can be used to control for sample quality.
authors.affiliation: metanomics GmbH, Berlin, Germany;
authors.forename: Beate
authors.initials: B
authors.lastname: Kamlage
authors.forename: Sandra González
authors.initials: SG
authors.lastname: Maldonado
authors.forename: Bianca
authors.initials: B
authors.lastname: Bethan
authors.forename: Erik
authors.initials: E
authors.lastname: Peter
authors.forename: Oliver
authors.initials: O
authors.lastname: Schmitz
authors.forename: Volker
authors.initials: V
authors.lastname: Liebenberg
authors.forename: Philipp
authors.initials: P
authors.lastname: Schatz
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001769:Blood / Q000378:metabolism*; D001800:Blood Specimen Collection / Q000379:methods* / Q000592:standards*; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods* / Q000592:standards*; D010949:Plasma / Q000378:metabolism; D011786:Quality Control; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers