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Correlation of the Capacity Factor in Vesicular Electrokinetic Chromatography with the Octanol: Water Partition Coefficient for Charged and Neutral Analytes

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Abstract

Purpose. The aim of this study was to develop a method based upon electrokinetic chromatography (EKC) using oppositely charged surfactant vesicles as a buffer modifier to estimate hydrophobicity (log P) for a range of neutral and charged compounds.

Methods. Vesicles were formed from cetyltrimethylammonium bromide (CTAB) and sodium n-octyl sulfate (SOS). The size and polydispersity of the vesicles were characterized by electron microscopy, dynamic light scattering, and pulsed-field gradient NMR (PFG-NMR). PFG-NMR was also used to determine if ion-pairing between cationic analytes and free SOS monomer occurred. The CTAB/SOS vesicles were used as a buffer modifier in capillary electrophoresis (CE). The capacity factor (log k′) was calculated by determining the mobility of the analytes both in the presence and absence of vesicles. Log k′ was determined for 29 neutral and charged analytes.

Results. There was a linear relationship between the log of capacity factor (log k′) and octanol/water partition coefficient (log P) for both neutral and basic species at pH 6.0, 7.3, and 10.2. This indicated that interaction between the cation and vesicle was dominated by hydrophobic forces. At pH 4.3, the log k′ values for the least hydrophobic basic analytes were higher than expected, indicating that electrostatic attraction as well as hydrophobic forces contributed to the overall interaction between the cation and vesicle. Anionic compounds could not be evaluated using this system.

Conclusion. Vesicular electrokinetic chromatography (VEKC) using surfactant vesicles as buffer modifiers is a promising method for the estimation of hydrophobicity.

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REFERENCES

  1. O. H. Chan and B. H. Stewart. Physicochemical and drug-delivery considerations for oral drug bioavailability. Drug Discovery Today 1:461-473 (1996).

    Google Scholar 

  2. T. Fujita, J. Iwasa, and C. Hansch. A new substituent constant, π, derived from partition coefficients. J. Am. Chem. Soc. 86:5175-5180 (1964).

    Google Scholar 

  3. W. P. Purcell, G. E. Bass, and J. M. Clayton. Strategy of Drug Design, Wiley, New York, 1973, pp. 126-143.

    Google Scholar 

  4. Y. Ishihama, Y. Oda, K. Uchikawa, and N. Asakawa. Correlation of octanol-water partition coefficients with capacity factors measured by micellar electrokinetic chromatography. Chem. Pharm. Bull. 42:1525-1527 (1994).

    Google Scholar 

  5. M. Adlard, G. Okafo, E. Meenan, and P. Camilleri. Rapid estimation of octanol-water partition coefficients using deoxycholate micelles in capillary electrophoresis. J. Chem. Soc., Chem. Commun. 2241-2243 (1995).

  6. B. J. Herbert and J. G. Dorsey. n-Octanol-water partition coefficient estimation by micellar electrokinetic capillary chromatography. Anal. Chem. 67:744-749 (1995).

    Google Scholar 

  7. J. T. Smith and D. V. Vinjamoori. Rapid determination of logarithmic partition coefficients between n-octanol and water using micellar electrokinetic capillary chromatography. J. Chromatogr. B 669:59-66 (1995).

    Google Scholar 

  8. S. Yang, J. G. Bumgarner, L. F. R. Kruk, and M. G. Khaledi. Quantitative structure-activity relationships studies with micellar electrokinetic chromatography: Influence of surfactant type and mixed micelles on estimation of hydrophobicity and bioavailability. J. Chromatogr. A 721:323-335 (1996).

    Google Scholar 

  9. M. Hanna, V. de Biasi, B. Bond, C. Salter, A. J. Hutt, and P. Camilleri. Estimation of the partitioning characteristics of drugs: A comparison of a large and diverse drug series utilizing chromatographic and electrophoretic methodology. Anal. Chem. 70:2092-2099 (1998).

    Google Scholar 

  10. Y. Ishihama, Y. Oda, K. Uchikawa, and N. Asakawa. Evaluation of solute hydrophobicity by microemulsion electrokinetic chromatography. Anal. Chem. 67:1588-1595 (1995).

    Google Scholar 

  11. Y. Ishihama, Y. Oda, and N. Asakawa. A hydrophobicity scale based on the migration index from microemulsion electrokinetic chromatography of anionic solutes. Anal. Chem. 68:1028-1032, (1996).

    Google Scholar 

  12. Y. Ishihama, Y. Oda, and N. Asakawa. Hydrophobicity of cationic solutes measured by electrokinetic chromatography with cationic microemulsions. Anal. Chem. 68:4281-4284, (1996).

    Google Scholar 

  13. K. Jinno and Y. Sawada. Relationships between capacity factors and hydropobicity of polycyclic aromatic hydrocarbons in cyclodextrin-modified micellar electrokinetic chromatography using surface treated capillaries. J. Liq. Chromatogr. 18:3719-3727 (1995).

    Google Scholar 

  14. M. G. Khaledi, S. C. Smith, and J. K. Strasters. Micellar electrokinetic capillary chromatography of acidic solutes: Migration behavior and optimization strategies. Anal. Chem. 63:1820-1830 (1991).

    Google Scholar 

  15. J. K. Strasters and M. G. Khaledi. Migration behavior of cationic solutes in micellar electrokinetic capillary chromatography. Anal. Chem. 63:2503-2508 (1991).

    Google Scholar 

  16. K. L. Herrington, E. W. Kaler, D. D. Miller, J. A. Zasadzinski, and S. Chiruvolu. Phase behavior of aqueous mixtures of dodecyltrimethylammonium bromide (DTAB) and sodium dodecyl sulfate (SDS). J. Phys. Chem. 97:13792-13802 (1993).

    Google Scholar 

  17. M. T. Yatcilla, K. L. Herrington, L. L. Brasher, E. W. Kaler, S. Chiruvolu, and J. A. Zasadzinski. Phase behavior of aqueous mixtures of cetyltrimethylammonium bromide (CTAB) sodium octyl sulfate (SOS). J. Phys. Chem. 100:5874-5879 (1996).

    Google Scholar 

  18. M. Hong, B. Weekley, S. J. Grieb, and J. P. Foley. Electrokinetic chromatography using thermodynamically stable vesicles and mixed micelles formed from oppositely charged surfactants. Anal. Chem. 70:1394-1403 (1998).

    Google Scholar 

  19. R. G. Bates. Determination of pH: Theory and Practice, Wiley, New York, 1964, pp. 219-220.

    Google Scholar 

  20. S. J. Gibbs and C. S. Johnson, Jr. A PFG NMR experiment for accurate diffusion and flow studies in the presence of eddy currents. J. Magn. Reson. 93:395-402 (1991).

    Google Scholar 

  21. D. Wu, A. Chen, and C. S. Johnson, Jr. An improved diffusion-ordered spectroscopy experiment incorporating bipolar-gradient pulses. J. Magn. Reson. Ser. A 115:260-264 (1995).

    Google Scholar 

  22. M. Lin, D. A. Jayawickrama, R. A. Rose, J. A. DelViscio, and C. K. Larive. Nuclear magnetic resonance spectroscopic analysis of the selective complexation of the cis and trans isomers of phenylalanylproline by β-cyclodextrin. Anal. Chim. Acta 307: 449-457 (1995).

    Google Scholar 

  23. K. F. Morris, B. J. Cutak, A. M. Dixon, and C. K. Larive. Analysis of diffusion coefficient distributions in humic and fulvic acids by means of diffusion ordered NMR spectroscopy. Anal. Chem. 71:5315-5321 (1999).

    Google Scholar 

  24. M. M. Bushey and J. W. Jorgenson. Effects of methanol-modified mobile phase on the separation of isotopically substituted compounds by micellar electrokinetic chromatography. J. Microcolumn Sep. 1:125-130 (1989).

    Google Scholar 

  25. W. S. Price. Pulsed-field gradient nuclear magnetic resonance as a tool for studying translational diffusion part I: Basic theory. Concepts Magn. Reson. 9:299-336 (1997).

    Google Scholar 

  26. S. W. Provencher. A constrained regularization method for inverting data represented by linear algebraic or integral equations. Comput. Phys. Commun. 27:213-227 (1982).

    Google Scholar 

  27. D. P. Hinton and C. S. Johnson, Jr. Diffusion ordered 2D NMR spectroscopy of phospholipid vesicles: Determination of vesicle size distributions. J. Phys. Chem. 97:9064-9072 (1993).

    Google Scholar 

  28. P. N. Craig. Cumulative subject index and drug compendium, Vol. 6. In C. Hansch, P. G. Sammes, and J. B. Taylor (eds.), Comprehensive Medicinal Chemistry, Pergamon Press, Oxford, 1990, pp. 237-965.

    Google Scholar 

  29. A. C. Moffat, J. V. Jackson, M. S. Moss, and B. Widdop (eds.). Clarke's Isolation and Identification of Drugs, The Pharmaceutical Press, London, 1986.

    Google Scholar 

  30. R. P. Austin, A. M. Davies, and C. N. Manners. Partitioning of ionizing molecules between aqueous buffers and phospholipid vesicles. J. Pharm. Sci. 84:1180-1183 (1995).

    Google Scholar 

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  1. Department of Chemistry, University of Kansas, Lawrence, Kansas, 66045

    J. L. Razak, B. J. Cutak, C. K. Larive & C. E. Lunte

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  1. J. L. Razak
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  4. C. E. Lunte
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Razak, J.L., Cutak, B.J., Larive, C.K. et al. Correlation of the Capacity Factor in Vesicular Electrokinetic Chromatography with the Octanol: Water Partition Coefficient for Charged and Neutral Analytes. Pharm Res 18, 104–111 (2001). https://doi.org/10.1023/A:1011039129664

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