Multi-wavelength spectrophotometric determination of the protolytic constants of tetracycline hydrochloride in some nonaqueous-water mixed solvents: a solvatochromism study.

Annihilation of the contribution of one chemical component from the original data matrix is a general method in rank annihilation factor analysis (RAFA). However, RAFA is not applicable for studying the protonation equilibria of multiprotic acids but in this study two-rank annihilation factor analysis (TRAFA) was used as an efficient chemometrics algorithm for determination of the protolytic constants (pKa) of tetracycline hydrochloride (TCHC) in some nonaqueous-water mixed solvents such as acetonitrile (AN)-water and methanol (MeOH)-water from the spectral pH-absorbance data. The spectral data was obtained from spectrophotometric acid-base titrations of different solutions of TCHC at (25.0±0.10)°C and an ionic strength of 0.10 M. In TRAFA algorithm the pKa values were obtained with relationship between residual standard deviation (R.S.D.) and hypothetical pKa values. In the case of TCHC, the spectra were divided in two consecutive subdivisions according to their pH range having two pKa and TRAFA was run twice. The validity of the obtained pKa values was checked with well-known chemometrics algorithms such as DATAN, EQUSPEC, SPECFIT/32 and SQUAD. The effects of changing solvent composition on the protolytic constants were explained by linear solvation energy relationships (LSER) utilizing solvatochromic parameters.