Generic MS-based method for the bioanalysis of therapeutic monoclonal antibodies in nonclinical studies.

A generic bioanalytical method was developed to quantify therapeutic IgG1 monoclonal antibodies (mAbs) in mouse sera by combining an easy sample preparation method with LC/MS using selected reaction monitoring. Rituximab and trastuzumab were used as model mAbs. A synthetic stable isotope-labeled peptide or a stable isotope-labeled mAb was used as an internal standard. The method feasibility was evaluated by a collaborative study involving six laboratories. The calibration curve ranged from 1.0 to 1000.0 μg/ml (correlation coefficient >0.99). The validation parameters including selectivity, linearity of calibration curve, accuracy and precision met the predefined acceptance criteria. Our method is a useful bioanalytical method for the quantification of therapeutic IgG mAbs in nonclinical animal studies.