Liquid Chromatography and Tandem Mass Spectrometery (LC-MS/MS).
Liquid chromatography (LC) coupled to tandem mass spectrometry, called LC-MS/MS or popularly known as LC-MS, is a powerful technique for analysis of proteins and peptides. The detection limit of few femtomoles in this technique makes it compatible fo0r detection of protein/peptides at low copy number per cell. In a typical LC-MS/MS experiment, the analyte is eluted by high performance liquid chromatography (HPLC) as applied elsewhere in protein chemistry; the only difference is that the dimension and flow rates are much smaller, achieved by nano-LC colums of internal diameter of 50-100 mm.

Complicated mixtures containing hundreds of proteins can be analyzed directly by this method even when concentrations of different proteins differ. LC-MS/MS can be used alone or in combination with 1-D or 2-D electrophoresis, immunoprecipitation, or protein purification tenchiques. In this manner, in a single LC-MS/MS run, a large number of peptides can be sequenced even if they have the same molecular weight but differ in hydrophobicity.