Quantitation and identification of dimers in co-formulations

A system comprising:

• a chromatographic column having a size-exclusion chromatography resin, wherein the chromatographic column is capable of receiving a mobile phase and a sample including a protein;
• an electrospray ionization mass spectrometer, wherein the electrospray ionization mass spectrometer is capable of being coupled online to said chromatographic column and wherein the electrospray ionization mass spectrometer is capable of being run under native conditions;
• and
• wherein the chromatographic column is further capable of being coupled to an ultraviolet detector using a splitter with at least three paths.

A method for quantifying a heterodimer species in a sample comprising a first protein and a second protein, said method comprising:

• immobilizing an antibody specific to the first protein on a solid surface;
• incubating the sample with said antibody;
• capturing a precipitated sample;
• collecting a flow through;
• treating the precipitated sample with a first compound;
• treating the flow through with a second compound;
• mixing the treated precipitated sample and at least a portion of the treated flow through to form a mixture;
• and
• analyzing the mixture using a liquid chromatography coupled to a mass spectrometer to quantify the heterodimer species in the sample.