The optimized dSPE method allowed to expand the coverage of chemical space representing blood products metabolome. The newly developed dSPE method was applied to enable the C18 RPC metabolic profiling of two exemplary cohorts of human plasma (MARS study, investigating acute and late radiation enteropathy ) and serum (BioAID and Microbial Products in Infection studies, to support the assessment of the host response in infection ) samples. The samples were additionally prepared using IPA protein precipitation and analyzed by C8 RPC tailored for lipid profiling. The metabolome coverage (Figure ) and analysis stability (Figure ) using the two complementary C18 and C8 RPC+/-methods as well as the system performance, robustness and high degree of analytical precision when analyzing dSPE prepared samples by C18 RPC+/-(Figure ) are exemplified using the serum pooled QC sample of the BioAID and Microbial Products in Infection studies. The tight clustering of the QC samples relative to the dispersion of the study samples on the PCA score plots demonstrates the instrument's stability and high quality of the acquired data.