Development of liquid chromatographic and UV-visible spectrophotometric methods for determination of pK(a) values of folic acid antimetabolites

Daldal Y. D., ÇUBUK DEMİRALAY E.

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, vol.212, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 212
  • Publication Date: 2022
  • Doi Number: 10.1016/j.jpba.2022.114647
  • Journal Name: JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Analytical Abstracts, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: Folic acid antimetabolites, pK(a) value, Acetonitrile-water mixtures, Acid-base equilibria, DISSOCIATION-CONSTANTS, IONIZABLE COMPOUNDS, CARBOXYLIC-ACIDS, RETENTION, SOLVATION, DRUGS, PREDICTION, RESOLUTION, MIXTURES
  • Süleyman Demirel University Affiliated: Yes

Abstract

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.