Thermal breakage of alkaloid ingredients was a common problem to which attention should be paid in the application of fruit ingredients separation. In this study, the mathematical models were established to predict the rejection of synephrine from Citrus aurantium L. (Rutaceae). The experiment showed that there was a linear relationship between operation pressure and membrane flux. Meanwhile, under the influence of solution–diffusion effect and the charge effect, the mass transfer coefficient was power functioned with initial concentration. The mathematical model showed that the predicted rejections of synephrine from Citrus aurantium extract were well approximate to real ones, and the lipid‐lowering active ingredient had effectively enriched. The predicted model of nanofiltration separation has a preferable applicability to synephrine and provides references for nanofiltration separation, especially for raw food materials with synephrine.