Application of ionic liquids for the determination of lipophilicity parameters using TLC method, and QSRR analysis for the antipsychotic drugs

BACKGROUND: Reversed-phase liquid chromatography may cause difficulties, especially in the case of basic drugs due to the strong silanophilic interactions in the partition mechanism. Recently, imidazolium-based ionic liquids additives appeared interesting and a convenient solution for suppressing noxious effect of free residuals of silanol groups, allowing remodeling the stationary/mobile-phase system, and thus improving lipophilicity assessment process. OBJECTIVE: The aim of the study was to evaluate insights into the retention behavior of basic antipsychotics using various RP-LC systems and compare them with data established from the modified ionic-liquids RP-TLC systems, and performing the QSRR analysis. METHOD: Retention and lipophilicity parameters of diverse antipsychotics have been examined in various RP-LC systems. Lipophilicity indices were compared with miscellaneous computed logP values. Furthermore, a large number of molecu¬lar descriptors has been computed and compared using various medicinal chemistry software, in order to contribute the analysis of QSRR. RESULTS: Designated correlation coefficients showed that lipophilicity parameters from TLC systems without [EMIM][BF4] additive correlates very poor with calculated logPs indices, whereas the indices from the traditional HPLC and TLC systems (with [EMIM][BF4]) were clearly better. Furthermore, QSRR analysis performed for these experimentally obtained lipophilicity parameters shown significant relationships between the retention constants (R_M^0, logkw) and the in silico calculated physicochemical molecular descriptors. CONCLUSION: ILs additive may be a significant factor affecting lipophilicity of basic compounds, thus their use may be favorable in lipophilicity assessment studies. QSRR models with ILs showed that they may be useful in searching/or predicting HPLC/TLC retention parameters for the new/other antipsychotic drugs.