# Defining Blood Plasma and Serum Metabolome by GC-MS
## 2 Serum and Plasma Metabolome as a \"Snapshot\" of a Human Biochemistry  
Blood and its components are the \"workhorses\" and favorite subjects for metabolomics analyses. For the query (blood metabolome) OR (plasma metabolome) OR (serum metabolome), the PubMed repository retrieves more than 16,000 articles published over the past 20 years. The dynamics of the increase in the number of papers is also staggering. If in 2008 fewer than a hundred studies on selected keywords were published, then in 2020, there are already more than 2000 publications. Such attractiveness of blood for metabolomic studies is due to the low invasiveness of its extraction. Blood is usually analyzed either as serum or plasma. The serum is a biological liquid obtained when whole blood coagulates. Coagulation is a vital process that prevents excessive blood loss from a minor wound. In a laboratory, it is common to centrifuge the coagulated blood to the bottom of the collection tube, leaving serum above the clot. The main components of serum are water, various proteins, peptides, amino acids, hormones, nitrogen compounds, various ions and salts, traces of nucleic acids, metabolites, and lipids. Plasma is the liquid component of blood, where coagulation has been prevented. It is obtained when a clotting-prevention agent (called anticoagulant) is added to whole blood and then placed in a centrifuge to separate the cellular material from the lighter liquid layer. Common anticoagulant agents are EDTA (ethylenediaminetetraacetic acid), heparin, and citrate. After centrifugation, the remaining plasma contains fibrinogen and other coagulation factors in their original state. From the biochemical point of view, plasma is practically identical to the liquid fraction of circulating blood (except for anticoagulants). It can be said that the main difference between plasma and serum is the presence of fibrinogen and coagulation proteins. Still, there are many other more subtle differences (e.g., in eicosanoids' levels [13; 14]). The nomadic nature of this biological fluid is also noteworthy. Blood's metabolic profile and components provide a global \"snapshot\" of the transformations of substances and energy occurring in all organs and tissues. The ability of the blood metabolome to reflect internal and external perturbations [15; 16] of the organism makes it one of the most important information layers for comprising a global picture of the condition of the individual at a specific point in time [17]. The versatility of the blood metabolome has provided fruitful ground for an impressive body of work investigating rapid [18; 19] and slow [20; 21] changes in the body. Modern metabolomic approaches allow the identification of characteristic patterns of low molecular weight compounds and associate them with the development of pathologies [22; 23; 24], lifestyle [25; 26], and eating habits [27; 28; 29] in both personalized mode [10; 30; 31] and large cohorts [32; 33]. Together, serum and plasma are the second most commonly used biofluids in metabolomic studies after urine [34] The preanalytical stages of blood processing are different for plasma and serum. Anticoagulants are added to plasma vacutainers, and coagulation enhancers are added to serum vacutainers. The question arises, are there any differences in the metabolomics of plasma and serum? If so, how do they affect the interpretation of obtained data? Studies show that none of the considered biological fluids has a clear advantage over the other in forming a representative metabolomic image of the object under investigation or the development of potential biomarkers [13; 35; 36]. Unless the primary plasma preparation looks more attractive: the processing is more reproducible and fast since there is no need to wait for the blood to clot, and clotting time may vary across individuals [37]. Another advantage of plasma over serum is the lower risk of hemolysis and thrombocytosis and the almost complete absence of post-centrifugal coagulation interference that can occur in serum.