The applicability and accuracy of isothermal titration calorimetry (ITC) to investigate intermolecular interactions in a high concentration domain applicable to liquid-liquid extraction (LLX) was studied for acid-base interactions. More accurate fits can be obtained using a sequential binding mechanism compared to a single reaction model, at the risk of finding a local minimum. Experiments with 0.24 M tri-n-octylamine (TOA) resulted in a residue of fit of 4.3% for the single reaction model, with a standard deviation σ of 1.6% in the stoichiometry parameter n, 12% in the complexation constant Kn,1, and 2.5% in the enthalpy Î"Hn,1. For the sequential model, σ was higher: 11% in K1,1, 26% in Kn+1,1, and 12% in Î"Hn+1,1. This study clearly showed that, at higher concentrations (order of moles per liter), accurate parameter estimation is possible and parameter values are concentration dependent. It is thus important to do ITC at the application concentration.