For bottom-up proteomics proteins are digested into smaller, easier to handle peptides, which are then separated by on-line HPLC and analyzed by the mass spectrometer (LC-MS).
It is critical to avoid/minimize any contaminations during your entire sample preparation that could interfere with the subsequent LC-MS analysis.
Salts, detergents and plasticisers are ionizable contaminations that cause major problems during the LC-MS analysis. They compete with the peptides binding to the column and detection by the mass spectrometer and thus will drastically decrease the overall sensitivity of the analysis.
Complex biological matrices may not only be rich in proteins but also rich in metabolites, lipids, nucleic acids, sugars, and other molecules. If not removed, they will also compete with the peptides for analysis.
Therefore, the primary goal should be to eliminate contamination and to increase the amount/number of peptides in a sample. If at all possible, systematic preventive elimination of contaminants is preferable over retrospective reduction of contaminants.
Equally important is an effective digestion protocol that produces few missed cleavages, few unspecific cleavages, and few undesired side reactions. If a peptide is present in properly cleaved,a missed cleaved and/or modified form, its signal intensity will be distributed into the number of forms present, decreasing its signal intensity and increasing the sample complexity (i.e. the number of detectable peptide ions). For example use of urea solution can lead to carbamylations (via its decomposition to ammonium cyanate) when using aged solutions or when used at elevated temperatures (above 25oC)
Avoid detergents that are not mass spec compatible, including:
Enzymatic Digestion Protocols
List of enzymes and specificity Expasy Peptide Cutter Page
List of digestion protocols
There are various chemical labeling strategies for concurrent peptide identification and multiplexed proteomics quantitation by mass spectrometry. Most quantitative proteomics reagents incorporate stable isotopes into the isobaric tag portion of the reagents and are used to label at the protein or peptide level. Check out their protocols, most start with the digestion followed by labeling:
List of peptide cleanup protocols for LC-MS