The thermodynamic dissociation constants of haemanthamine, lisuride, metergoline and nicergoline by the regression analysis of spectrophotometric data

The mixed dissociation constants of four drugs - haemanthamine, lisuride, metergoline and nicergoline - at various ionic strengths I of range 0.01 and 0.6 and at temperatures of 25 °C and 37 °C were determined using SPECFIT32 and SQUAD(84) regression analyses of the pH-spectrophotometric titration data. A proposed strategy for 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 haemanthamine. 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. The thermodynamic dissociation constant pKaT was estimated by non-linear regression of {pKa, I} data at 25 °C and 37 °C: for haemanthamine pKaT=7.22(1) and 7.05 (2), for lisuride pKaT=7.87(1) and 7.59 (1), for metergoline pKaT=7.62(1) and 7.38 (1), for nicergoline pKa,1T=7.94(1) and 7.69 (1). Goodness-of-fit tests for various regression diagnostics enabled the reliability of the parameter estimates to be found.