Development of liquid chromatographic and UV-visible spectrophotometric methods for determination of pKa values of folic acid antimetabolites

In this study, the values of ionization/protonation constants (pK(a)) of pemetrexed and raltitrexed, which are folic acid antimetabolites, were determined by reversed-phase liquid chromatography (RPLC) and UV-visible spectrophotometric methods at 25 degrees C. The (s)(s)pK(a) values were evaluated by retention time (t(R)) in binary acetonitrile-water mixtures with acetonitrile (ACN) contents of 13%, 15%, 17% and 20% (v/v) for the RPLC method and 13%, 15% and 17% (v/v) for the spectrophotometric method. The aqueous pK(a) values ((w)(w)pK(a)) of the studied compounds were calculated from the (s)(s)pK(a) value using the macroscopic parameters (mole fraction and dielectric constant), which play an important role in solvent properties. In addition, the degree of ionization of pemetrexed and raltitrexed was calculated using the (w)(w)pK(a) values.

Automated summary

In this study, the pK(a) values of pemetrexed and raltitrexed were determined by RPLC and UV-visible spectrophotometric methods. The aqueous pK(a) values were calculated using macroscopic parameters, and the degree of ionization was also calculated.