The thermodynamic dissociation constants of losartan, paracetamol, phenylephrine and quinine by the regression analysis of spectrophotometric data

The mixed dissociation constants of four drug acids - losartan, paracetamol, phenylephrine and quinine - at various ionic strengths I of range 0.01 and 1.0 and at temperatures of 25 and 37 °C were determined using SPECFIT32 and SQUAD(84) regression analysis of the pH-spectrophotometric titration data. A proposed strategy of efficient experimentation in a dissociation constants determination, followed by a computational strategy for the chemical model with a dissociation constants determination, is presented on the protonation equilibria of losartan. Indices of precise methods predict the correct number of components, and even the presence of minor ones when the data quality is high and the instrumental error is known. Improved identification of the number of species uses the second or third derivative function for some indices, namely when the number of species in the mixture is higher than 3 and when, due to large variations in the indicator values even at logarithmic scale, the indicator curve does not reach an obvious point where the slope changes. The thermodynamic dissociation constant pKaT was estimated by nonlinear regression of {pKa, I} data at 25 and 37 °C: for losartan pKa,1T=3.63(1) and 3.57(3), pKa,2T=4.84(1) and 4.80(3), for paracetamol pKa,1T=9.78(1) and 9.65(1), for phenylephrine pKa,1T=9.17(1) and 8.95(1), pKa,2T=10.45(1) and 10.22(1), for quinine pKa,1T=4.25(1) and 4.12(1), pKa,2T=8.72(1) and 8.46(2). Goodness-of-fit tests for various regression diagnostics enabled the reliability of the parameter estimates to be found.