Rafał Sochacki, Małgorzata Dołowy
Application of different methods to predict the lipophilicity parameter of danazol
2021-12-17
The aim of this study was to evaluate the applicability of both methods, i.e. reversed-phase thin-layer chromatography (RP-TLC) and high-performance thin-layer chromatography (RP-HPTLC), and computational algorithms to determine the lipophilicity parameter of danazol. The values of the theoretical partition coefficients expressed as AlogPs, AClogP, AlogP, MlogP, XlogP2, XlogP3, SKlogP, and logP were obtained using different computational algorithms. The mean value of logP for danazol (logPśr) was also determined based on these data, which is 4.01 ± 0.51. The most similar theoretical values of the partition coefficient were SKlogP (4.16), MlogP (4.15), and logP (4.08), respectively, which were calculated using CS Chem 3D Ultra 7.0 software. Chromatographic lipophilicity parameter (RMW) of danazol was determined according to the Soczewinski-Wachtmeister equation using different stationary phases in the form of chromatographic plates: RP2F254, RP8F254, RP18F254, RP18WF254, and the following mobile phases: methanol-water, acetonitrile-water, 1,4-dioxane-water, and acetone-water. The organic modifier content in these phases was 50–95%. The effects of mobile and stationary phases as well as computational algorithms on the differences in the values of chromatographic lipophilicity parameter and theoretical logP value of danazol, respectively, were observed. The highest similarity in RMW values of danazol was obtained using RP2F254 and RP18WF254 chromatographic plates and using acetone-water and 1,4-dioxane-water as mobile phases, respectively. On the other hand, the results of chromatographic lipophilicity parameter i.e. RMW were most similar to the mean value of logP in the case of RP8F254 plates developed with methanol and water (RMW = 4.111 ± 0.214) and RP18F254 plates analyzed with acetone-water mobile phase (RMW = 4.169 ± 0.379), respectively.
The studies carried out in this work show the usefulness of thin-layer chromatography and selected computational algorithms to determine the lipophilicity parameter of danazol, which may be applied in the future to study the bioavailability of this compound and its derivatives.
Keywords: TLC, danazol, lipophilicity, logP.
© Farm Pol, 2021, 77(10): 601–607