Numerous commercially available SPE materials exist for the depletion of lipids from blood product samples prior to UHPLC-MS analysis. These materials are most often applied in targeted quantitative analyses where any unintended depletion effects on the analytes of interest can be directly tested during method development and validation, which is impossible in downstream assessment of the global LMWM profile . In addition, SPE-based sample preparation in untargeted metabolomics can have the potential risk of selectively remove LMWMs, introduce contaminants, be time-and resourceconsuming, and suffer from lower reproducibility in large-scale analyses . Still, these solutions, when used in conjunction with the manufacturer's recommended protocols, represent a valuable reference point against which our proposed dSPE methodology was evaluated.