Usefulness of reversed-phase HPLC enriched with room temperature imidazolium based ionic liquids for lipophilicity determination of the newly synthesized analgesic active urea derivatives

• Published in: Journal of pharmaceutical and biomedical analysis 2012-07, Vol.66, p.58-67
• Main Authors: Flieger, Jolanta, Czajkowska-Żelazko, Anna, Rządkowska, Marzena, Szacoń, Elżbieta, Matosiuk, Dariusz
• Format: Article
• Language: English
• Subjects: Analgesics - chemistry; Analysis; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Fundamental and applied biological sciences. Psychology; General pharmacology; Hydrophobic and Hydrophilic Interactions; Imidazoles - chemistry; Ionic liquids; Ionic Liquids - chemistry; Lipophilicity determination; Medical sciences; Micelles; Partition coefficient; Pharmacology. Drug treatments; RP-HPLC; Solvents - chemistry; Surface-Active Agents - chemistry; Temperature; Urea - analogs & derivatives; Urea - chemistry; Urea derivatives
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2012.02.025

Lipophilicity of several novel analgesic active 1-(1-arylimidazolidyn-2-ylidyn)-3-arylalkyl urea derivatives has been estimated by the use of chromatographic method. The investigated compounds were analyzed by reversed-phase high performance liquid chromatography (RP-HPLC) using mixtures of methanol or acetonitrile and water with addition of imidazolium based room temperature ionic liquids varying in an anion chaotropicity as the mobile phases. The relationships between log k values vs. concentration of organic solvent was used for determination of the log kw values by extrapolation technique. The partition coefficients (log P) values were calculated by means of the Pallas 3.1.1.2. and Spartan 10.0 softwares and further correlated with log kw measured experimentally in classical organic–aqueous eluent system and systems modified with ionic liquids addition. It was found that log kw values measured in eluent system modified with butyl-methyl imidazoilum chloride correlate the best with the logarithm of partition coefficient calculated by Pallas software (log Pcalc.). Furthermore, it was found that the examined compounds form H-bonding with imidazoilum cation of modifiers improving the chromatographic peak parameters (the symmetry factor, the theoretical plates number) especially when ionic liquid's anion was more chaotropic. Amphiphilic ionic liquid possessing longer alkyl chain substituent (OMIM BF4) can be considered as a new cationic surfactant. Micellar conditions improved separation selectivity of chloro- and methoxy substituted derivatives.