Protein digestion kits are noted to reduce time by combining several procedural steps (e.g. reduction, digestion, peptide clean-up) in a single tube. The inclusion of peptide clean-up steps allows digests to proceed in the presence of detergents making these methods particularly attractive to the study of cell and tissue proteomes. Although independent comparisons of variability and effectiveness of “single pot” or “suspension trapping” methods versus conventional methods have been published for cells, comparative data are less available for undepleted serum which is dominated by high abundance proteins.