DETERMINATION OF OCTANOL-WATER PARTITION COEFFICIENT OF NOVEL COUMARIN BASED ANTICANCER COMPOUNDS BY REVERSED-PHASE ULTRA-FAST LIQUID CHROMATOGRAPHY
DOI:
https://doi.org/10.22159/ijpps.2017v9i8.19128Keywords:
RP-UFLC, Synthetic, Coumarin, Log P, Octanol-WaterAbstract
Objective: The present study aims at the development of a reversed phase ultra-fast liquid chromatography (RP-UFLC) method for measurement of the lipophilicity (log P) between n-octanol and water for the newly synthesized coumarin derivatives in our laboratory.
Methods: The synthesized compounds were dissolved in methanol and analyzed using XTerra RP18 column as the stationary phase and a mixture of methanol (0.25% v/v octanol) and buffer as the mobile phase with isocratic elution.
Results: In this study we concentrated on the relationship between a reversed-phase ultra-fast liquid chromatography (RP-UFLC) retention parameters and log P of our synthesized compounds. Furthermore, a good correlation and very close values were obtained between the experimentally determined log P values and values obtained from Chemdraw.
Conclusion: The developed method was found to be insensitive to any of the impurities present and moreover it requires very little sample for analysis.
Downloads
References
Dixit GR, Mathur VB. Microemulsions: platform for improvement of solubility and dissolution of poorly soluble drugs. Asian J Pharm Clin Res 2015:8:7-17.
Dearden JC. Partitioning and lipophilicity in quantitative structure-activity relationships. Environ Health Perspect 1985; 61:203-28.
Leo A, Hansch C, Elkins CD. Partition coefficients and their uses. Chem Rev 1971;71:525-615.
Smith DA, Jones BC, Walker DK. Design of drugs involving the concepts and theories of drug metabolism and pharma-cokinetics. Med Res Rev 1996;16:243-66.
Kumar SS, Anjali T. In silico design and molecular docking studies of some 1, 2-benzisoxazole derivatives for their analgesic and anti-inflammatory activity. Int J Curr Pharm Res 2017;9:38-41.
Testa B, Crivori P, Reist M, Carrupt PA. The influence of lipophilicity on the pharmacokinetic behavior of drugs: concepts and examples. Perspect Drug Discovery Des 2000;19:179-221.
Monika D, Małgorzata S, Jerzy S. Lipophilicity study of some non-steroidal anti-inflammatory agents and cephalosporin antibiotics: a review. Talanta 2011;86:35-51.
Leo A, Hansch C, Elkins D. Partition coefficients and their use. Chem Rev 1971;71:525-616.
Miller JM, Blackburn AC, Shi Y, Melzak AJ, Ando HY. Semi-empirical relationships between effective mobility, charge, and molecular weight of pharmaceuticals by pressure-assisted capillary electrophoresis: applications in drug discovery. Electrophoresis 2002;23:2833-41.
Matoga M, Laborde-Kummer E, Langlois MH, Dallet P, Bosc JJ, Jarry C, et al. Determination of pKa values of 2-amino-2-oxazolines by capillary electrophoresis. J Chromatogr A 2003; 984:253-60.
Poole SK, Patel S, Dehring K, Workman H, Poole CF. Determination of acid dissociation constants by capillary electrophoresis. J Chromatogr A 2004;1037:445-54.
Hatem OA, Suhail FSA, Amer Mousa Juda AM. Determination of physicochemical and geometrical properties of some carvedilol derevitives. Asian J Pharm Clin Res 2016;9:330-6.
Tetko IV. Computing chemistry on the web. Drug Discovery Today 2005;15:1497-500.
Viswanadhan VN, Ghose AK, Revankar GR, Robins RK. Atomic physicochemical parameters for three dimensional structure directed quantitative structure―activity relationships. IV: Additional parameters for hydrophobic and dispersive interactions and their application for an automated superposition of certain naturally occurring nucleoside antibiotics. J Chem Inf Comput Sci 1989;29:163–72.
Tate PA, Dorsey JG. Column selection for liquid chromatographic estimation of the k'w hydrophobicity parameter. J Chromatogr A 2004;1042:37-48.
Karger BL, Gant JR, Hartkopf A, Weiner PH. Hydrophobic effects in reversed-phase liquid chromatography. J Chromatogr 1976;128:65-78.
Lombardo F, Shalaeva MY, Tupper KA, Gao F, Abraham MH. ElogPoct: a tool for lipophilicity determination in drug discovery. J Med Chem 2000;43:2922-8.
Marshall DB, McKenna WP. Deuterium nuclear magnetic resonance relaxation study of mobile phase-stationary phase interactions in reversed-phase high-performance liquid chromatography. Anal Chem 1984;56:2090-3.
Valko´ K, Bevan C, Reynold D. Chromatographic hydrophobicity index by fast-gradient RP-HPLC: a high-throughput alternative to log P/log D. Anal Chem 1997;69:2022-9.
Lambert WJ. Modeling oil-water partitioning and membrane permeation using reversephase chromatography. J Chromatogr A 1993;656:469-84.
Braurnann T, Grapper TH, Damm L, Grimme LH. Function of chlorophylls and carotenoids in thylakoid membranes. Pigment bleaching in relation to PS-I and PSII activity of subchloroplast particles prepared with digitonin. Adv Photosynth Res 1984;2:137-40.
Harnisch M, Mockel HJ, Schulze GJJ. Releationship between log P shake-flask values and capacity factors derived from reversed phase high performance liquid chromatography for n-alkyl benzene and some OECD reference substances. Chromatography 1983;282:315-28.
Poâ€Chang C, Kimberly F Marie W, Chingâ€Chiang S, Denise P. Medium throughput p Kadeterminations of drugs and chemicals by reverse phase HPLC with an organic gradient. J Liq Chromatogr Relat Technol 2006;29:2291-301.
Venkata SK, Gurupadayya BM, Vishwanathan BI, Chandan RS, Nagesha DK. Cytotoxicity studies of coumarin analogs: design, synthesis and biological activity. RSC Adv 2016;6:98816–28.
Lombardo F, Shalaeva MY, Tupper KA, Gao F, Abraham MH. ElogPoct: a tool for lipophilicity determination in drug discovery. J Med Chem 2000;27:43:2922-8.
https://www.drugbank.ca/drugs/DB00997. [Last accessed on 13 Apr 2017].
Published
How to Cite
Issue
Section
