In this work, we developed and optimized a C18 dSPE-based method that simultaneously depletes lipids and proteins from blood products with a minimal perturbance to the LMWM composition. The proposed approach is rapid, inexpensive, and fit for large-scale deployment. Using this method, we were able to apply an established C18 RPC method developed for large-scale human urine metabolic profiling to the measurement of LMWMs in blood products, leveraging a singular in-house metabolite annotation resource. Together with an established C8 lipidomic profiling , the two RPC methods cover a broad range of the blood metabolome with robust analytical performance.