Solvent Effects on p<i>K</i>_aValues of Some Anticancer Agents in Acetonitrile–Water Binary Mixtures

Abstract

The solute–solvent interactions of four anticancer drugs, daunorubicin, doxorubicin, vincristine sulfate, and 6-thioguanine, have been studied in acetonitrile–water mixtures up to 50 % acetonitrile by volume fraction using a UV/pH titration method. The acidity constants have been calculated with the STAR (stability constants by absorbance readings) program. The interactions between the four anticancer drugs and the solvent studied, acetonitrile–water mixtures, was identified using the microscopic parameters (Kamlet and Taft’s solvatochromic parameters: α, β, and π*). The Kamlet and Taft general equation for pKa1 and pKa2 values of 6-thioguanine, doxorubicin, daunorubicin, and vincristine sulfate was reduced to two terms (the independent term and the hydrogen-bond-donating ability, α) or three terms (the independent term, polarity/polarizability, π*, and the hydrogen-bond-donating ability, α) using linear regression analysis in acetonitrile–water mixtures. The Kamlet and Taft equations can be used to predict the acidity constants of daunorubicin, doxorubicin, vincristine sulfate, and 6-thioguanine at any acetonitrile composition, which would be helpful in practical work during chromatographic method development.