Title:Application of Ionic Liquids for the Determination of Lipophilicity Parameters Using TLC Method, and QSRR Analysis for the Antipsychotic Drugs
Volume: 16
Issue: 7
Author(s): Dominik Mieszkowski, Marcin Koba and Michał P. Marszałł*
Affiliation:
- Department of Medicinal Chemistry, Faculty of Pharmacy, Collegium Medicum of Nicolaus Copernicus University, 85- 089, Bydgoszcz,Poland
Keywords:
Antipsychotic drugs, lipophilicity parameters, molecular descriptors, QSRR, quantitative structure-retention relationships,
retention parameters.
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 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.