The Problem of Dynamic Ranges

A well-known problem in the analysis of protein mixtures is the fact that the presence of components with high abundance may prevent even the detection (let alone quantification) of low-abundance proteins (which could ordinarily be 

Low-abundance, low-molecular mass proteins or drugs in plasma/serum 

Albumin, a major constituent in serum (60-80 mg/L), is known to act as a transport carrier for small proteins. Also, many antineoplastic drugs bind to albumin, often at the 80-95% level. Removal or depletion of albumin is a major problem there are problems with ultrafiltration (e.g., membrane binding of small proteins and drugs) and other approaches, e.g., Cibacron dye columns and immunoaffinity-based protein subtraction chromatography. Albumin removal using acetonitrile may be a simple alternative [54] however, there is no truly satisfying method at this time. 

Several techniques have been developed for quantification using stable isotope dilution [57]. There are special considerations for the global addition of stable isotope labels before or after protein digestion, and the metabolic labeling of proteins in vivo, e.g., growing cells or even whole animals in which all proteins have been 

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