Chromatographic analysis and pKa evaluation of active pharmaceutical ingredients in anti-metastatic breast cancer: Green vs. conventional RPLC

Abstract

This study aimed to determine the chromatographic retention and dissociation/protonation constant (pK_a) values of lapatinib and tamoxifen, key drugs used in metastatic breast cancer treatment, at 37°C using both conventional and green high-performance liquid chromatography (HPLC) methods. Qualitative analysis was conducted on an XTerra C18 column (250 ×4.6 mm I.D., 5 μm particle size) at a flow rate of 1 mL/min. Hydroorganic mixtures with 45 %, 50 %, 55 %, and 60 % (v/v) organic modifiers were used to evaluate the retention times of the compounds. The compatibility of pK_a values $\left({}_s{}^s\mathrm{pK}_a\right)$ of the compounds in water-organic solvent mixtures obtained from these studies, which were carried out without any significant change in liquid chromatography performance, with the values obtained by the conventional method is remarkable. The ${}_s{}^s\mathrm{pK}_a$ values determined in this study were correlated with the macroscopic parameters of acetonitrile, methanol, ethanol and the pK_a (${}_w{}^w\mathrm{pK}_a)$values of lapatinib and tamoxifen in water were calculated. The ${}_w{}^w\mathrm{pK}_a$ values calculated from these studies are compatible with each other and with the literature values. The environmental impact of the study, which was carried out using the green method and the conventional RPLC method, was evaluated using the Green Solvent Selection Tool (GSST), Green Analytical Procedures Index (GAPI), and Analytical Greenness Metric Approach (AGREE).