Non-compartmental analysis (NCA) is regarded as the standard for establishing bioequivalence, despite its limitations and the existence of alternative methods such as non-linear mixed effects modelling (NLMEM). Comparisons of NCA and NLMEM in bioequivalence testing have been limited to drugs with one-compartment kinetics and have included a large number of different approaches. A simulation tool was developed with the ability to rapidly compare NCA and NLMEM methods in determining bioequivalence using both R and NONMEM and applied to a drug with two-compartment pharmacokinetics. Concentration-time profiles were simulated where relative bioavailability, random unexplained variability (RUV) at the lower limit of quantification (LLOQ) differed between simulations. NLMEM analyses employed either the M1 or M3 methods for dealing with values below the LLOQ. It was used to elucidate the impact of changes in (i) RUV at the LLOQ, (ii) the extent of censoring data below the LLOQ and (iii) the concentration sampling times. The simulations showed NLMEM having a consistent 20-40% higher accuracy and sensitivity in identifying bioequivalent studies when compared to NCA, while NCA was found to have a 1-10% higher specificity than NLMEM. Increasing data censoring by increasing the LLOQ resulted in decreases of ~10% to the accuracy and sensitivity of NCA, with minimal effects on NLMEM. The tool provides a platform for comparing NCA and NLMEM methods and its use can be extended beyond the scenarios reported here. In the situations examined it is seen that NLMEM is more accurate than NCA and may offer some advantages in the determination of bioequivalence.