Immobilized Artificial Membrane (lAM)-HPLC for Partition Studies of Neutral and Ionized Acids and Bases in Comparison with the Liposomal Partition System

Springer Science and Business Media LLC - 1999
Cornelia Ottiger, Heidi Wunderli-Allenspach1
1Biopharmacy, Department of Pharmacy, ETH Zürich, Zurich, Switzerland

Tóm tắt

Purpose. To study the partitioning of model acids ((RS)-warfarin and salicylic acid), and bases (lidocaine, (RS)-propranolol and diazepam), with immobilized artificial membrane (lAM)-HPLC, as compared to partitioning in the standardized phosphatidylcholine liposome/buffer system. Methods. The pH-dependent apparent partition coefficients D were calculated from capacity factors (k′IAM) obtained by IAM-HPLC, using a 11-carboxylundecylphosphocholine column. For lipophilic compounds k′IAM, values were determined with organic modifiers and extrapolation to 100% water phase (k′IAMw) was optimized. Temperature dependence was explored (23 to 45° C), and Gibbs free energy (ΔG), partial molar enthalpy (ΔH) and change in entropy (ΔS) were calculated. Equilibrium dialysis was used for the partitioning studies with the liposome/buffer system. Results. For extrapolation of k′IAMw, linear plots were obtained both with the respective dielectric constants and the mole fractions of the organic modifier. All tested compounds showed a similar pH-D diagram in both systems; however, significant differences were reproducibly found in the pH range of 5 to 8. In all cases, ΔG and ΔH were negative, whereas ΔS values were negative for acids and positive for bases. Conclusions. In both partitioning systems, D values decreased significantly with the change from the neutral to the charged ionization state of the solute. The differences found under physiological conditions, i.e. around pH 7.4, were attributed to nonspecific interactions of the drug with the silica surface of the IAM column.

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Tài liệu tham khảo

L. Herbette, A. M. Katz, and J. M. Sturtevant. Comparisons of the interaction of propranolol and timolol with model and biological membrane systems. Mol. Pharmacol. 24:259-269 (1983).

R. P. Mason, D. G. Rhodes, and L. G. Herbette. Reevaluating equilibrium and kinetic binding parameters for lipophilic drugs based on a structural model for drug interaction with biological membranes. J. Med. Chem. 34:869-877 (1991).

G. V. Betageri and J. A. Rogers. Thermodynamics of partitioning of β-blockers in the n-octanol-buffer and liposome systems. Int. J. Pharm. 36:165-173 (1987).

G. M. Pauletti and H. Wunderli-Allenspach. Partition coefficients in vitro: artificial membranes as a standardized distribution model. Eur. J. Pharm. Sci. 1:273-282 (1994).

C. Pidgeon and U. V. Venkataram. Immobilized artificial membrane chromatography: supports composed of membrane lipids. Anal. Biochem. 176:36-47 (1989).

S. Ong, H. Liu, X. Qiu, G. Bhat, and C. Pidgeon. Membrane partition coefficients chromatographically measured using immobilized artificial membrane surfaces. Anal. Chem. 67:755-762 (1995).

D. Rhee, R. Markovich, W. G. Chae, X. Qiu, and C. Pidgeon. Chromatographic surfaces prepared from lyso phosphatidylcholine ligands. Anal. Chim. Acta 297:377-386 (1994).

J. J. Michels and J. G. Dorsey. Retention in reversed-phase liquid chromatography: solvatochromic investigation of homologous alcohol-water binary mobile phases. J. Chromatogr. 457:85-98 (1988).

J. G. Dorsey and M. G. Khaledi. Hydrophobicity estimations by reversed-phase liquid chromatography. Implications for biological partitioning processes. J. Chromatogr. A 656:485-499 (1993).

S. Ong and C. Pidgeon. Thermodynamics of solute partitioning into immobilized artificial membranes. Anal. Chem. 67:2119-2128 (1995).

L. A. Cole and J. G. Dorsey. Temperature dependence of retention in reversed-phase liquid chromatography. 1. Stationary-phase considerations. Anal. Chem. 64:1317-1323 (1992).

C. Ottiger and H. Wunderli-Allenspach. Partition behaviour of acids and bases in a phosphatidylcholine liposome-buffer equilibrium dialysis system. Eur. J. Pharm. Sci. 5:223-231 (1997).

T. Teorell and E. Stenhagen. Ein Universalpuffer für den pH-Bereich 2.0 bis 12.0. Biochem. Z. 299:416-419 (1938).

H. H. Landolt and R. L. Börnstein. Elektrische Eigenschaften I. Band 2, Springer Verlag, Stuttgart, 1960.

P. S. Albright and L. J. Gosting. Dielectric constants of the methanol-water system from 5 to 55°. J. Am. Chem. Soc. 68:1061-1063 (1946).

G. Kortüm, S. D. Gokhale and H. Wilski. Über Leitfähigkeitsmessungen an Tetraäthylammoniumjodid in Lösungsmittelgemischen. Z. Physik. Chem., Neue Folge 4:286-296 (1955).

H. S. Harned and B. B. Owen. The physical chemistry of electrolytic solutions. Reinhold Publishing Corporation, New York, 1958.

K. Hartke, H. Hartke, E. Mutschler, G. Ruecker and M. Wichtl. DAB 10: Deutsches Arzneibuch, Kommentar. Wissenschaftliche Verlagsgesellschaft, Stuttgart, 1991.

C. Pidgeon, S. Ong, H. Choi, and H. Liu. Preparation of mixed ligand immobilized artificial membranes for predicting drug binding to membranes. Anal. Chem. 66:2701-2709 (1994).

S. D. Krämer and H. Wunderli-Allenspach. The pH-dependence in the partitioning behaviour of (RS)-[3H]Propranolol between MDCK cell lipid vesicles and buffer. Pharm. Res. 13:1851-1855 (1996).

S. D. Krämer, C. Jakits-Deiser, and H. Wunderli-Allenspach. Free fatty acids cause pH-dependent changes in drug-lipid membrane interactions around physiological pH. Pharm. Res. 14:827-832 (1997).

S. D. Krämer, A. Braun, C. Jakits-Deiser, and H. Wunderli-Allenspach. Towards the predictability of drug-lipid membrane interactions: the pH-dependent affinity of propranolol to phosphatidylinositol containing liposomes. Pharm. Res. 15:739-744 (1998).

R. J. Markovich, X. Qiu, D. E. Nichols, C. Pidgeon, B. Invergo, and F. M. Alvarez. Silica subsurface amine effect on the chemical stability and chromatographic properties of end-capped immobilized artificial membrane surfaces. Anal. Chem. 63:1851-1860 (1991).

P. Schindler and H. R. Kamber. Die Acidität von Silanolgruppen. Helv. Chim. Acta 51:1781-1786 (1968).

Y. Guo, G. A. Imahori, and L. A. Colon. Hydrolytically stable amino-silica glass coating material for manipulation of the electroosmotic flow in capillary electrophoresis. J. Chromatogr. A 744:17-29 (1996).

J. W. Dolan and L. R. Snyder. Troubleshooting LC systems: a comprehensive approach to troubleshooting LC equipment and separations. Humana Press, Clifton, NJ, 1989.

A. Avdeef, K. J. Box, J. E. A. Comer, C. Hibbert, and K. Y. Tam. pH-metric logP 10. Determination of liposomal membrane-water partition coefficients of ionizable drugs. Pharm. Res. 15:209-215 (1998).

F. Barbato, M. I. La Rotonda, and F. Quaglia. Interactions of nonsteroidal antiinflammatory drugs with phospholipids: Comparison between octanol/buffer partition coefficients and chromatographic indexes on immobilized artificial membranes. J. Pharm. Sci. 86:225-229 (1997).

J. B. Hasted, D. M. Ritson, and C. H. Collie. Dielectric properties of aqueous ionic solutions. Parts I and II. J. Chem. Physics 16:1-21 (1948).

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