•Global retention models are developed and fitted for highly complex samples•Common column/solvent and specific solute parameters are obtained by regression•Guidelines to develop experimental designs facilitating peak tracking are given•Comparison of global and individual retention models for selected components•Method was applied to extracts of medicinal plants with diverse characteristics We report here the improvement of a procedure to obtain global models, able to describe the retention behaviour of several sample components simultaneously. The reported global models include parameters that account for the general effects of column and solvent on retention and are common for all components, whereas other parameters are specific of each sample component. These models are fitted by alternate regression and offer a prediction performance comparable to individual retention models. The approach is suitable to samples of natural products including a large number of components in extremely diverse concentrations and in the absence of standards. Guidelines are given for the successful development of sample-oriented experimental designs (i.e. adapted to the elution of the components of the natural products), constituted by multi-linear gradients. These designs also facilitate peak tracking. The model proposed by Neue and Kuss to describe the retention was found to yield the best predictions. The approach is applied to the extracts of samples of green tea, lemon balm and linden, yielding excellent predictions of retention for selected components.