Thermodynamic Dissociation Constants of Rasagiline by the Nonlinear Regression and Factor Analysis of Multiwavelength Spectrophotometric pH Titration Data

The mixed dissociation constants of rasagiline-free base [N-propargyl-1-(R)aminoindan] and rasagiline mesylate {[N-propargyl-1-(R)aminoindan]methansulfonate} at different ionic strengths I in the range of (0.01 and 0.4) mol·L -1 and at temperatures of (25 and 37) °C were determined with the use of two different multiwavelength and multivariate treatments of spectral data, SPECFIT32 and SQUAD(84), nonlinear regression analyses, and INDICES factor analysis. Concurrently, the experimental determination of the thermodynamic dissociation constants was combined with their computational prediction of the PALLAS program based on knowledge of the chemical structures of the drug in good agreement with its experimental value. The factor analysis in the INDICES program predicts the correct number of light-absorbing components, when the data quality is high and the instrumental error is known. Most indices always predict the correct number of components when the signal-to-error ratio (SER) is higher than 10. The thermodynamic dissociation constant pK a T was estimated by nonlinear regression of pK a and I data: for rasagiline base, pK a T = 7.12(1) at 25 °C and 7.01(1) at 37 °C; for rasagiline mesylate, pK a T = 7.07(1) at 25 °C and 7.16(1) at 37 °C, where the value in parentheses is the standard deviation in the last significant digit. The reliability of the dissociation constants of both drugs was proven with goodness-of-fit tests of the multiwavelength spectrophotometric pH titration data.