This study reports the use of modelling software for the successful method development of IgG1 cysteineconjugated antibody drug conjugate (ADC) in RPLC. The goal of such a method is to be able to calculate theaverage drug to antibody ratio (DAR) of and ADC product. A generic method development strategy wasproposed including the optimization of mobile phase temperature, gradient profile and mobile phaseternary composition. For the first time, a 3D retention modelling was presented for large therapeuticprotein. Based on a limited number of preliminary experiments, a fast and efficient separation of theDAR species of a commercial ADC sample, namely brentuximab vedotin, was achieved. The predictionoffered by the retention model was found to be highly reliable, with an average error of retention timeprediction always lower than 0.5% using a 2D or 3D retention models. For routine purpose, four to six initialexperiments were required to build the 2D retention models, while 12 experiments were recommendedto create the 3D model. At the end, RPLC can therefore be considered as a good method for estimatingthe average DAR of an ADC, based on the observed peak area ratios of RPLC chromatogram of the reducedADC sample.