Controlling pre-analytical process in human serum/plasma metabolomics

Metabolome analysis is a key component of serum/plasma metabolomics studies for clinical and biological applications. There are several steps involved, including pre-analytical, analytical and data processing procedures. With recent advances in sensitive analytical tools and sophisticated data analysis software, careful control of the pre-analytical process becomes critical for generating reliable and reproducible quantitative results. Due to the great diversity of chemicals present in serum/plasma, controversial findings on the extent of pre-analytical effects were not uncommon. This is mainly caused by different analytical methods used in the reported studies with varying quantification accuracies, numbers of metabolites detected, and sample sizes used. In this review, we describe how each pre-analytical step may affect metabolome analysis. Instead of merely surveying the reported studies, we discuss the reported findings with careful consideration of the methods used to avoid or minimize the tendency to generalize a study's finding to a board effect on metabolome analysis.