Analytical and Bioanalytical Chemistry

, Volume 406, Issue 25, pp 6203–6211 | Cite as

Analysis of drug interactions with very low density lipoprotein by high-performance affinity chromatography

Research Paper
First Online:
Received:
Revised:
Accepted:

Abstract

High-performance affinity chromatography (HPAC) was utilized to examine the binding of very low density lipoprotein (VLDL) with drugs, using R/S-propranolol as a model. These studies indicated that two mechanisms existed for the binding of R- and S-propranolol with VLDL. The first mechanism involved non-saturable partitioning of these drugs with VLDL, which probably occurred with the lipoprotein’s non-polar core. This partitioning was described by overall affinity constants of 1.2 (±0.3) × 106 M−1 for R-propranolol and 2.4 (±0.6) × 106 M−1 for S-propranolol at pH 7.4 and 37 °C. The second mechanism occurred through saturable binding by these drugs at fixed sites on VLDL, such as represented by apolipoproteins on the surface of the lipoprotein. The association equilibrium constants for this saturable binding at 37 °C were 7.0 (±2.3) × 104 M−1 for R-propranolol and 9.6 (±2.2) × 104 M−1 for S-propranolol. Comparable results were obtained at 20 and 27 °C for the propranolol enantiomers. This work provided fundamental information on the processes involved in the binding of R- and S-propranolol to VLDL, while also illustrating how HPAC can be used to evaluate relatively complex interactions between agents such as VLDL and drugs or other solutes.

Keywords

Very low density lipoprotein Propranolol Drug-protein binding High-performance affinity chromatography Frontal analysis 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This work was supported by the National Institute of Health under grant R01 GM044931 and was performed in facilities renovated under grant RR015468-01.

Supplementary material

216_2014_8081_MOESM1_ESM.pdf (24 kb)
ESM 1 (PDF 23 kb)

References

  1. 1.
    Otagiri M (2005) Drug Metab Pharmacokinet 20:309–323CrossRefGoogle Scholar
  2. 2.
    Bertucci C, Domenici E (2002) Curr Med Chem 9:1463CrossRefGoogle Scholar
  3. 3.
    Patel S, Wainer IW, Lough JW (2006) In: Hage DS (ed) Handbook of affinity chromatography, 2nd edn. CRC, Boca Raton, pp 663–683Google Scholar
  4. 4.
    Hage DS, Jackson A, Sobansky M, Schiel JE, Yoo MY, Joseph KS (2009) J Sep Sci 32:835–853CrossRefGoogle Scholar
  5. 5.
    Xuan H, Hage DS (2005) Anal Biochem 346:300–310CrossRefGoogle Scholar
  6. 6.
    Mallik R, Xuan H, Guiochon G, Hage DS (2008) Anal Biochem 376:154–156CrossRefGoogle Scholar
  7. 7.
    Jonas A (2002) In: Vance DE, Vance JE (eds) Biochemistry of lipids, lipoproteins, and membranes. Elsevier, Amsterdam, pp 483–504CrossRefGoogle Scholar
  8. 8.
    Hage DS (2002) J Chromatogr B 768:3–30CrossRefGoogle Scholar
  9. 9.
    Kuroda Y, Cao B, Shibukawa A, Nakagawa T (2001) Electrophoresis 22:3401–3407CrossRefGoogle Scholar
  10. 10.
    Sobansky MR, Hage DS (2012) Anal Bioanal Chem 403:563–571CrossRefGoogle Scholar
  11. 11.
    Shen Q, Wang L, Zhou H, Jiang H, Yu L, Zeng S (2013) Acta Pharmacol Sin 34:998–1006CrossRefGoogle Scholar
  12. 12.
    Noctor TAG (1993) In: Wainer IW (ed) Drug Stereochemistry: analytical methods and pharmacology. CRC/Marcel Dekker, New York, pp 337–364Google Scholar
  13. 13.
    Dong H, Guo X, Li Z (2011) In: Lin G, You Q, Cheng J (eds) Chiral drugs: chemistry and biological action. Wiley, Hoboken, pp 347–380CrossRefGoogle Scholar
  14. 14.
    Glasson S, Zini R, D’Athis P, Tillement JP, Boissier JR (1980) Mol Pharmacol 17:187–191Google Scholar
  15. 15.
    Ohnishi T, Mohamed NAL, Shibukawa A, Kuroda Y, Nakagawa T, El Gizawy S, Askal HF, El Kommos ME (2002) J Pharm Biomed Anal 27:607–614CrossRefGoogle Scholar
  16. 16.
    Mohamed NAL, Kuroda Y, Shibukawa A, Nakagawa T, El Gizawy S, Askal HF, El Kommos ME (2000) J Chromatogr A 875:447–453CrossRefGoogle Scholar
  17. 17.
    Mohamed NAL, Kuroda Y, Shibukawa A, Nakagawa T, El Gizawy S, Askal HF, El Kommos ME (1999) J Pharm Biomed Anal 21:1037–1043CrossRefGoogle Scholar
  18. 18.
    Hebb AR, Godwin TF, Gunton RW (1968) Can Med Assoc J 98:246–251Google Scholar
  19. 19.
    Hansson L, Malmerona R, Olander R, Rosenhall L, Westerlund A, Aberg H, Hood B (1972) Klein Wschr 50:364–369CrossRefGoogle Scholar
  20. 20.
    Harrison DC, Griffin JR, Fiene TJ (1965) N Engl J Med 273:410–415CrossRefGoogle Scholar
  21. 21.
    Henry JA, Dunlop AW, Mitchell SN, Turner P, Adams P (1981) J Pharm Pharmacol 33:179–182CrossRefGoogle Scholar
  22. 22.
    Plumb RS, Potts WB III, Rainville PD, Alden PG, Shave DH, Baynham G, Mazzeo JR (2008) Rapid Commun Mass Spectrom 22:2139–2152CrossRefGoogle Scholar
  23. 23.
    Barklay M (1972) In: Nelson GJ (ed) Blood Lipids and lipoproteins: quantitation, composition, and metabolism. Wiley, New York, pp 587–603Google Scholar
  24. 24.
    Wasan KM, Cassidy SM (1998) J Pharm Sci 87:411–424CrossRefGoogle Scholar
  25. 25.
    Harmony JAK, Aleson AL, McCarthy BM (1986) In: Scanu AM, Spector AA (eds) Biochemistry and biology of plasma lipoproteins. Marcel Dekker, New York, pp 403–430Google Scholar
  26. 26.
    Mbewu AD, Durrington PN (1990) Atherosclerosis 85:1–14CrossRefGoogle Scholar
  27. 27.
    Durrington PN (1989) In: Durrington PN (ed) Lipoproteins and lipids. Wright, London, pp 255–277Google Scholar
  28. 28.
    Havel RJ, Kane JP (1995) In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, Vogelstein B (eds) The metabolic and molecular basis of inherited disease. McGraw-Hill, New York, pp 1129–1138Google Scholar
  29. 29.
    Skipski VR (1972) In: Nelson GJ (ed) Blood Lipids and lipoproteins quantitation, composition, and metabolism. Wiley, New York, pp 471–583Google Scholar
  30. 30.
    Kwong TC (1985) Clin Chim Acta 151:193–216CrossRefGoogle Scholar
  31. 31.
    Chen S, Sobansky M, Hage DS (2010) Anal Biochem 397:107–114CrossRefGoogle Scholar
  32. 32.
    Kim HS, Wainer IW (2008) J Chromatogr B 870:22–26CrossRefGoogle Scholar
  33. 33.
    Hollósy F, Valkó K, Hersey A, Nunhuck S, Kéri G, Bevan C (2006) J Med Chem 49:6958–6971CrossRefGoogle Scholar
  34. 34.
    Buchholz L, Cai CH, Andress L, Cleton A, Brodfuehrer J, Cohen L (2002) Eur J Pharm Sci 15:209–215CrossRefGoogle Scholar
  35. 35.
    Loun B, Hage DS (1994) Anal Chem 66:3814–3822CrossRefGoogle Scholar
  36. 36.
    Hage DS, Chen J (2006) In: Hage DS (ed) Handbook of affinity chromatography. CRC/Taylor & Francis, New York, pp 595–628Google Scholar
  37. 37.
    Tweed S, Loun B, Hage DS (1997) Anal Chem 69:4790–4798CrossRefGoogle Scholar
  38. 38.
    Mallik R, Xuan H, Hage DS (2007) J Chromatogr A 1149:294–304CrossRefGoogle Scholar
  39. 39.
    Yang CY, Gu ZW, Valentinova N, Pownall HJ, Lee B, Yang M, Xie YH, Guyton JR, Vlasik TN, Fruchart JC, Gotto AM (1993) J Lipid Res 34:1311–1321Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Chemistry DepartmentUniversity of NebraskaLincolnUSA

Personalised recommendations