Magnetite nanoparticles (MNPs) have been considered for a number of applications in drug delivery. However, the main challenge is to assure high cell-penetration levels, especially when dealing with cargoes that show limited membrane passing. A strategy is to encapsulate the MNPs into liposomes to form magnetoliposomes (MLs) capable of fusing with membranes to achieve high delivery rates. Magnetoliposomes have therefore been used as carriers in the biomedical field due to their ability to release active molecules that can be used in treatments of diverse diseases. There are several techniques to produce such encapsulates, however, the main challenge is that the process often leads to an important fraction of non-encapsulated MNPs. Purification of such a fraction is challenging because of the small size difference between the particles and the MLs and the reduced magnetic responsiveness. Seeking to obtain pure MLs with potential use in the medical field, the following study presents finite element simulations using COMSOL Multiphysics of two purification methods. Accordingly, we implemented magnetic separation and asymmetric pinched flow fractionation separation to evaluate their purification efficiencies in light of operation parameters such as the Flow Rate Ratio (FRR) and Total Velocity Ratio (TVR). Additionally, a mixture interaction approach was used to model the MNPs as a dispersed ferrofluid phase. This was compared with a particle tracing approach where MNPs are considered individual entities subjected to hydrodynamic forces. The results show efficiencies between 60% and 90% for both separation methods, which confirms their feasibility to improve and optimize the purification of MLs in a high throughput manner.