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 (RO>M, 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.
