Authors:Costas Giaginis and Anna Tsantili-Kakoulidou
The reversed-phase TLC retention behavior of 26 structurally diverse basic and neutral drugs has been investigated under different chromatographic conditions by varying the aqueous component and pH of the mobile phase. Phosphate buffer, phosphate-buffered saline, morpholinepropanesulfonic acid at pH 7.4, phosphate buffer at pH 11.0, and pure water were used with different proportions of methanol as the mobile phase. Use of
-octanol as mobile phase additive was also investigated. Different sets of extrapolated
values were compared and the effect of electrolytes on retention is discussed. Retention was correlated with lipophilicity log
. Use of log
with an ionization correction term
at pH 7.4 led to good correlation and confirmed a reduced effect of protonation on retention. Finally, linear solvation energy relationships were established for all data sets. Apart from the reduced effect of ionization, hydrogen-bond basicity and volume were found to effect to an almost equal extent octanol-water partitioning and RPTLC retention under all conditions at pH 7.4, indicating close similarity between the different processes. At pH 11 a lower negative contribution of hydrogen-bond basicity to retention compared with noctanol water partitioning, was noticed.
Authors:Costas Giaginis, Demetris Dellis, and Anna Tsantili-Kakoulidou
The reversed-phase TLC retention behavior of a series of structurally diverse drugs, mostly basic compounds, has been investigated with different aqueous mobile-phase components. Phosphate buffer, phosphate-buffered saline, and morpholinepropanesulfonic acid, with or without addition of
-decylamine, at pH 7.4, and phosphate buffer at pH 11.0 were used with different proportions of methanol as the mobile phase. The effect of the buffer constituents on extrapolated
values and the corresponding slopes,
, and their interrelationship, was evaluated. The different sets of
values were correlated with lipophilicity log
. MOPS was found to be more suitable than phosphate buffer for assessment of lipophilicity. Use of log
instead of log
, combined with use of the ionization-correction term
, led to improved correlation and revealed a reduced net effect of ionization on retention.
Authors:Marios Chrysanthakopoulos, Ioannis Nicolaou, Vassilis Demopoulos, and Anna Tsantili-Kakoulidou
The lipophilicity of a series of pyrrolyl-acetic acid derivatives, inhibitors of the aldose reductase enzyme, was assessed by reversedphase thin layer chromatography (RP-TLC). The role of the carbon content of the stationary phase in reproducing the octanol-water partitioning was examined using RP-18F254S and RP-8F254S plates. Retention on RP-8 plates was found to be more uniform, while these plates exhibit some advantages for the lipophilicity assessment of acidic compounds, compared to the most commonly used RP-18 plates. However, in both cases, different energetics between octanol-water partitioning and RP-TLC retention seem to be involved. On both plates the influence of ionization of the acid functional group was found to be more pronounced on retention in comparison with previous findings for basic compounds. Both sets of RMw values were compared with HPLC chromatographic indices, reported previously. They were found to correlate better with logkw values, if the latter have been determined in the presence of noctanol as mobile phase additive. In all cases, best relationships were obtained with RMw(C18). The performance of RMw indices in regression equations modeling the aldose reductase inhibitory activity was evaluated. Results were comparable with those previously generated using logP. Both RMw(C8) and RMw(C18) proved to perform equally well as lipophilicity indices in correlating biological activity, if combined with the ionization correction term Q and Abraham’s basicity term B as additional parameters.