Surfactant deep eutectic solvents for extraction and HPLC-PDA analysis of antipsoriatic drugs in spiked water and lipophilic topical matrices.
Alamir Samy G SG, Magdy Nancy N, Ibrahim Adel Ehab AE, Hussein Lobna A LA et al.
Deep eutectic solvents (DESs) have garnered attention in various disciplines due to their unique properties. In this work, different surfactants were screened as hydrogen-bond acceptors in combination with structurally related phenols as hydrogen-bond donors (HBDs), and successful and unsuccessful pairings were discussed. Literature on successfully paired surfactants was also reviewed. Nevertheless, the screening results and reported classifications, together with the observed aqueous behavior and variable extraction performance across different matrices, prompted further investigation of composition-behavior relationships of these systems. Five surfactant-phenolic DESs were synthesized by mixing o-cresol (CRS) or catechol with dodecyltrimethylammonium bromide (DTAB), cetyltrimethylammonium bromide (CTAB), or Brij35 at 75.0 °C for 30.0 min. Although more hydrophobic HBDs were used than in previous studies, the resulting DESs displayed transient aqueous dispersion after vortexing and subsequently re-separated on standing. Their viscosity (64.21-1389 mPa s) and conductivity (1.00-447.00 μS/cm) also varied. 1H/13C nuclear magnetic resonance and Fourier-transform infrared spectroscopy indicated hydrogen bonding between phenolic hydroxyl groups and bromide/ether acceptors, with features suggesting π-cation association in cationic-surfactant systems. To probe their practicality, a high-performance liquid chromatography method with photodiode array detection was developed for betamethasone valerate, halobetasol propionate, fusidic acid, and tazarotene, achieving separation within 6 min, and compared with five reported chromatographic methods. Validation per the International Council for Harmonisation Q2 (R1) guidelines demonstrated linearity (R2 0.9997-0.9999), accuracy (98.2-102.4%), and precision (≤2.0%), with robustness evaluated through experimental design. Brij35-based systems showed reduced extraction recoveries for lipophilic topical formulations. After additional screening, CRSCTAB and CRSDTAB DESs were used with spiked water samples as a hydrophilic proof-of-concept matrix, employing salting-out-assisted liquid-liquid microextraction using ammonium acetate. The results suggest provisional amphiphilic-like rather than conventional hydrophobic-DES behavior; however, thermal phase diagrams, equilibrium water-solubility measurements, and broader thermodynamic investigations remain necessary before any formal reclassification.