Wioletta Parys, Joanna Mularczyk

Application of thin layer chromatography and theoretical methods to assess the lipophilic properties of metamizole, propyphenazone and nimesulide

 

2024-11-20

Subject of research. The lipophilicity of chemical compounds influences their absorption, distribution, metabolism, excretion, and toxicity. It is therefore extremely helpful in designing new structures of potential therapeutic substances, as well as in the process of optimizing already used compounds (drugs) in order to obtain better parameters. The assessment of lipophilic properties of compounds is a complex process and requires the use of both experimental (e.g., chromatographic) and theoretical (computational) methods. Chromatographic methods are currently the most popular indirect experimental methods for determining the lipophilicity of drugs (estimating the logP value).

In clinical practice, the most commonly prescribed group of drugs are analgesics. Metamizole, propyphenazone and nimesulide are analgesics that have been known for several decades, and are relatively cheap and widely available. In the scientific literature, there have been no studies described to date regarding the assessment of the lipophilicity of the above-mentioned analgesics using both methods, i.e. reversed-phase thin-layer chromatography/high-performance thin-layer chromatography RP-TLC/HPTLC and theoretical methods using different computational algorithms. In this work, in addition to the commonly determined chromatographic lipophilicity parameter R_MWS based on the Soczewiński-Wachtmeister’s method, an additional chromatographic lipophilicity parameter R_MWO was also determined based on the Ościk’s equation.

Aim. The aim of the study was to assess the possibility of using both methods, i.e. experimental RP-TLC/HPTLC and theoretical (computational) methods to determine the lipophilic properties of metamizole, propyphenazone and nimesulide. The R_MWS and R_MWO values obtained for the examined compounds were then compared with the theoretical logP values obtained using different calculation algorithms and the logPexp values determined experimentally in the n-octanol-water system.

Material and methods. Solutions of the analyzed compounds at a concentration of 1 mg/mL were prepared in methanol for metamizole and propyphenazone and in acetone for nimesulide. The mobile phases used were mixtures of methanol with water, dioxane with water, acetonitrile with water, and acetone with water with different contents of organic modifiers, changing every 5% in the case of RP-8F₂₅₄ and RP-18F₂₅₄ plates and every 10% in the case of RP-18WF₂₅₄ plates. The R_M parameter values obtained by the RP-TLC/HPTLC method in different chromatographic systems, i.e. four mobile phases (methanol-water, dioxane-water, acetonitrile-water, acetone-water) and three stationary phases (RP-8F₂₅₄, RP-18F₂₅₄, RP-18WF₂₅₄) were used to determine the chromatographic lipophilicity parameters according to the Soczewiński-Wachtmeister’s equation (R_MWS) and the Ościk’s equation (R_MWO). The R_MWS and R_MWO values obtained for the studied compounds were then compared with the theoretical parameters (AlogPs, AClogP, AlogP, MlogP, xlogP2, xlogP3, miLogP, logP_KOWWIN, ACD/logP) and the experimental value of the partition coefficient (logP_exp).

Results. It was found that metamizole has the lowest, while nimesulide has the highest lipophilicity. There is no data on the logP_exp value for metamizole and variations in the theoretical values of the logP partition coefficients are observed. The parameter closest to the experimentally determined logP_exp for propyphenazone is the theoretical parameter AlogPs and the chromatographic lipophilicity parameters, i.e., R_MWO(DRP18), R_MWO(DRP8), R_MWO(ARP18W), R_MWS(MRP18W) and R_MWS(ARP8). Moreover, values close to logP_exp and AlogPs show the chromatographic lipophilicity parameters R_MWS(MRP18W) and R_MWS(ARP8). The parameter closest to the experimentally determined logP_exp for nimesulide is the theoretical parameter xlogP3 and the chromatographic lipophilicity parameters, i.e., R_MWS(ARP18), R_MWS(ACNRP18) and R_MWS(MRP8). In addition, theoretical partition coefficients such as AlogPs, xlogP2 and AlogP have similar values.

Conclusions. The simple, fast and cost-effective RP-TLC/HPTLC technique and the lipophilicity parameters marked as R_MWS and R_MWO can be successfully used as alternative to classical extraction in the n-octanol-water system in describing the lipophilic nature of metamizole, propyphenazone and nimesulide. They may be used in the future in the process of their optimization in order to obtain better parameters, e.g., bioavailability of the examined compounds and their derivatives, and may also be useful in the process of designing new and more therapeutically effective preparations or derivatives of metamizole, propyphenazone and nimesulide.

RP-TLC/HPTLC and internet databases have been shown to be useful tools in determining the lipophilicity of biologically active compounds, including metamizole, propyphenazone, and nimesulide. Additionally, chemometric techniques have been shown to be helpful in assessing the lipophilicity of metamizole, propyphenazone, and nimesulide determined using different methods.

Keywords: TLC, non-opioid analgesics, non-steroidal anti‑inflammatory drugs, Soczewiński-Wachtmeister’s equation, Ościk’s equation.

© Farm Pol, 2024, 80(6): 355–365