Agnieszka Kusztal, Małgorzata Dołowy, Katarzyna Bober Majnusz

Comparison of the lipophilicity parameters of drospirenone and lynestrenol

The aim of this study was the chromatographic analysis of two steroid compounds; drospirenone and lynestrenol, representing the group of pro- and gestagens, respectively, and their application to determine the lipophilicity parameters of both these compounds. Various chromatographic systems were tested, consisting of silica gel plates coated with RP18F254 and RP18WF254, and three binary mixtures as mobile phases, such as methanol-water, acetonitrile-water and propan-2-ol-water with an organic modifier contained in each of them ranging from 50% to 90% or from 40% to 90%, respectively. The RF values of drospirenone and lynestrenol obtained through numerous chromatographic analyzes, which were then converted into the values of the RM parameter, were used to determine the experimental value of the lipophilicity parameter of these compounds in the form of RMW. In addition, the obtained chromatographic parameters of lipophilicity were compared with the theoretical values of the partition coefficient (logP) of drospirenone and lynestrenol obtained on the basis of various calculation algorithms in the form of AlogP, AlogPs, AClogP, MlgP, xlogP2 and xlogP3 and, respectively, with the experimental logP value marked as logPexp available for one of them i.e. drospirenone. As a result of the chromatographic tests and analysis of all parameter results lipophilicity, the usefulness of thin-layer chromatography in the applied systems consisting of RP18F254 and RP18WF254 plates and mobile phases composed of methanol-water, acetonitrile-water, and propan-2-ol-water for determining the experimental value of the lipophilicity parameter of drospirenone and lynestrenol in the form of RMW was confirmed. Moreover, the research presented in the paper shows that selected topological indexes of biologically active compounds, including those with a steroidal structure, such as drospirenone and lynestrenol, may be valuable in determining the correlation between their structure and properties, including lipophilic properties. It was found that the new formula proposed in the above work for calculating the theoretical value of the lipophilicity parameter in the form of logPx, which is based on the values of selected topological indices, such as the Balaban index (B) and the Molecular Topological Index (M), is an interesting example of the use of indices based on various calculation algorithms for determining the lipophilicity parameter of the tested steroids.

Keywords:  TLC, drospirenone, lipophilicity, logP, lynestrenol, topological indices.

© Farm Pol, 2022, 78(10): 571–579

Comparison of the lipophilicity parameters of drospirenone and lynestrenol

654.74 kB | 29 grudnia 2022