Abstract: The invention relates to a novel method for determining the amount of an antibody of interest in a biological sample. In one embodiment, the method of the invention is characterized in that it comprises at least a step of protein depletion of said biological sample by pepsin digestion to produce F(ab)2 fragments. In a preferred embodiment, one ore more peptides identifying the sequence of the antibody of interest is monitored using high-performance liquid chromatography with tandem mass spectrometry detection (HPLC-MS/MS).