Determination of lipophilicity of novel potential antituberculotic agents using HPLC on monolithic stationary phase and theoretical calculations

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 48; no. 2; pp. 310 - 314
• Main Authors: MRKVICKOVA, Z, KOVARIKOVA, P, BALIKOVA, S, KLIMES, J
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier B.V 29.09.2008; Elsevier Science
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Antitubercular Agents - chemistry; Biological and medical sciences; Chemical software; Chromatography, High Pressure Liquid - methods; Fundamental and applied biological sciences. Psychology; General pharmacology; HPLC; Lipophilicity; Medical sciences; Monolithic column; Partition coefficient; Pharmacology. Drug treatments; Solubility; Chemical software; Partition coefficient; Lipophilicity; HPLC; Monolithic column; HPLC chromatography; Theoretical study; Antituberculous agent; Software; Determination; Quantitative analysis; Stationary phase
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2007.12.040

The HPLC analyses on the monolithic stationary phase were employed for rapid determination of lipophilicity of the two sets of newly synthesized potential antituberculotic agents. The analyses utilized the mixture of methanol and phosphate buffer (pH 7.4) as a mobile phase and a flow rate of 4 mL/min. Monolithic stationary phase enabled to significantly reduce the time of analyses, achieve appropriate peak shapes for all tested compounds as well as the separation of positional isomers. Furthermore, the theoretical lipophilic parameters (log P) for all compounds were calculated employing the chemical programs (e.g., ACD/logP, HyperChem, miLogP, AlogP, KOWWIN and COSMOFrag, etc.). The experimental data (log k) and calculated log P values were compared by linear regression analysis. The highest correlation for both series was obtained for KOWWIN and miLogP programs. However, capability of particular chemical software to precisely predict lipophilicity of a compound is structurally dependent. Thus the predictive power of the selected program should be verified using experimental method. The results of this study documented that experimental determination of lipophilicity using HPLC on monolithic stationary phase is practical and reasonable for this purpose.