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Application of Ionic Liquids for the Determination of Lipophilicity Parameters Using TLC Method, and QSRR Analysis for the Antipsychotic Drugs

Author(s):

Dominik Mieszkowski, Marcin Koba and Michał Piotr Marszałł*   Pages 1 - 12 ( 12 )

Abstract:


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.

Keywords:

antipsychotic drugs, lipophilicity parameters, molecular descriptors, QSRR, quantitative structure-retention relationships, retention parameters

Affiliation:

Department of Medicinal Chemistry, Faculty of Pharmacy, Collegium Medicum of Nicolaus Copernicus University, 85-094 Bydgoszcz, Department of Toxicology, Faculty of Pharmacy, Collegium Medicum of Nicolaus Copernicus University, 85-094 Bydgoszcz, Department of Medicinal Chemistry, Faculty of Pharmacy, Collegium Medicum of Nicolaus Copernicus University, 85-094 Bydgoszcz



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