Pre-analytical and analytical variability in absolute quantitative MRM-based plasma proteomic studies

Quantitative plasma proteomics, through the use of targeted MRM-MS and isotopically labeled standards, is emerging as a popular technique to address biological- and biomedical-centered queries. High precision and accuracy are essential in such measurements, particularly in protein biomarker research where translation to the clinic is sought. Standardized procedures and routine performance evaluation of all stages of the workflow (both pre-analytical and analytical) are therefore imperative to satisfy these requisites and enable high inter-laboratory reproducibility and transferability. In this review, we first discuss the pre-analytical and analytical variables that can affect the precision and accuracy of 'absolute' quantitative plasma proteomic measurements. Proposed strategies to limit such variability will then be highlighted and unmet needs for future exploration will be noted. Although there is no way to conduct a truly comprehensive review on this broad, rapidly changing topic, we have highlighted key aspects and included references to review articles on various sub-topics.