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Medicinal Chemistry


ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Research Article

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 P. Marszałł*

Volume 16, Issue 7, 2020

Page: [848 - 859] Pages: 12

DOI: 10.2174/1573406415666190723162959

Price: $65


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 the harmful effect of free residuals of silanol groups, allowing remodeling of the stationary/mobile-phase system, and thus improving the lipophilicity assessment process.

Objective: The aim of the study was to evaluate the retention behavior of basic antipsychotics using various RP-LC systems, and compare them with data obtained from the modified ionic-liquids RP-TLC systems, and perform the QSRR analysis.

Methods: 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 molecular descriptors have been computed and compared using various medicinal chemistry software, in order to contribute to the analysis of QSRR.

Results: Designated correlation coefficients showed that lipophilicity parameters from TLC systems without [EMIM][BF4] additive correlates very poor with the 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 showed significant relationships between the retention constants (ROM, logkw) and the in silico calculated physicochemical molecular descriptors.

Conclusion: ILs additive may be a significant factor affecting the 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.

Graphical Abstract
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