Applications of multiple reaction monitoring targeted proteomics assays in human plasma

Introduction: Multiple (or selected) reaction monitoring-mass spectrometry (MRM/SRM) is a targeted proteomic method that can be used for relative and absolute quantification. Multiple reports exist supporting the potential of the approach in proteomic biomarker validation. Areas covered: To get an overview of the applications of MRM in protein quantification in plasma, a search in MedLine/PubMed was performed using the keywords: 'MRM/SRM plasma proteomic/proteomics/proteome'. The retrieved studies were further filtered to focus on disease biomarkers and the main results are summarized. Expert opinion: MRM is increasingly employed for the quantification of both well-established but also newly discovered putative biomarkers and occasionally their post-translationally modified forms in plasma. Fractionation is regularly required for the detection of low abundance proteins. Standardized procedures to facilitate assay establishment and marker quantification have been proposed and, in few cases, implemented. Nevertheless, in most cases, absolute quantification is not performed. To advance, multiple technical issues including the regular use of standard labeled peptides and appropriate quality controls to monitor assay performance should be considered. Additionally, clinical aspects involving careful study design to address biomarker clinical use should also be considered.