title: Metabolomic Quality Assessment of EDTA Plasma and Serum Samples.
abstract: Handling and processing of blood can significantly alter the molecular composition and consistency of biobank samples and can have a major impact on the identification of biomarkers. It is thus crucial to identify tools to determine the quality of samples to be used in biomarker discovery studies. In this study, a non-targeted gas chromatography/time-of-flight mass spectrometry (GC-TOFMS) metabolomic strategy was used with the aim of identifying quality markers for serum and plasma biobank collections lacking proper documentation of preanalytical handling. The effect of postcentrifugation delay was examined in serum stored in tubes with gel separation plugs and ethylenediaminetetraacetic acid (EDTA) plasma in tubes with or without gel separation plugs. The change in metabolic pattern was negligible in all sample types processed within 3 hours after centrifugation regardless of whether the samples were kept at 4°C or 22°C. After 8 and 24 hours postcentrifugation delay before aliquoting, there was a pronounced increase in the number of affected metabolites, as well as in the magnitude of the observed changes. No protective effect on the metabolites was observed in gel-separated EDTA plasma samples. In a separate series of experiments, lactate and glucose levels were determined in plasma to estimate the effect of precentrifugation delay. This separate experiment indicates that the lactate to glucose ratio may serve as a marker to identify samples with delayed time to centrifugation. Although our data from the untargeted GC-TOFMS analysis did not identify any specific markers, we conclude that plasma and serum metabolic profiles remain quite stable when plasma and serum are centrifuged and separated from the blood cells within 3 hours.
authors.affiliation: 1 Swedish Metabolomics Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå University , Umeå, Sweden .
authors.forename: Linus
authors.initials: L
authors.lastname: Malm
authors.affiliation: 2 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm, Sweden .
authors.forename: Gunnel
authors.initials: G
authors.lastname: Tybring
authors.affiliation: 1 Swedish Metabolomics Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå University , Umeå, Sweden .
authors.forename: Thomas
authors.initials: T
authors.lastname: Moritz
authors.affiliation: 3 Clinical Chemistry, Department of Laboratory Medicine, Karolinska University Hospital , Stockholm, Sweden .
authors.forename: Britta
authors.initials: B
authors.lastname: Landin
authors.affiliation: 4 Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University , Uppsala, Sweden .
authors.forename: Joakim
authors.initials: J
authors.lastname: Galli
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000737:chemistry; D001800:Blood Specimen Collection / Q000592:standards; D004492:Edetic Acid / Q000494:pharmacology*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry / Q000187:drug effects*; D011786:Quality Control; D044967:Serum / Q000737:chemistry / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D004492:Edetic Acid
keywords: delayed processing of serum; metabolomics; plasma