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.
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References
Otagiri M (2005) Drug Metab Pharmacokinet 20:309–323
Bertucci C, Domenici E (2002) Curr Med Chem 9:1463
Patel S, Wainer IW, Lough JW (2006) In: Hage DS (ed) Handbook of affinity chromatography, 2nd edn. CRC, Boca Raton, pp 663–683
Hage DS, Jackson A, Sobansky M, Schiel JE, Yoo MY, Joseph KS (2009) J Sep Sci 32:835–853
Xuan H, Hage DS (2005) Anal Biochem 346:300–310
Mallik R, Xuan H, Guiochon G, Hage DS (2008) Anal Biochem 376:154–156
Jonas A (2002) In: Vance DE, Vance JE (eds) Biochemistry of lipids, lipoproteins, and membranes. Elsevier, Amsterdam, pp 483–504
Hage DS (2002) J Chromatogr B 768:3–30
Kuroda Y, Cao B, Shibukawa A, Nakagawa T (2001) Electrophoresis 22:3401–3407
Sobansky MR, Hage DS (2012) Anal Bioanal Chem 403:563–571
Shen Q, Wang L, Zhou H, Jiang H, Yu L, Zeng S (2013) Acta Pharmacol Sin 34:998–1006
Noctor TAG (1993) In: Wainer IW (ed) Drug Stereochemistry: analytical methods and pharmacology. CRC/Marcel Dekker, New York, pp 337–364
Dong H, Guo X, Li Z (2011) In: Lin G, You Q, Cheng J (eds) Chiral drugs: chemistry and biological action. Wiley, Hoboken, pp 347–380
Glasson S, Zini R, D’Athis P, Tillement JP, Boissier JR (1980) Mol Pharmacol 17:187–191
Ohnishi T, Mohamed NAL, Shibukawa A, Kuroda Y, Nakagawa T, El Gizawy S, Askal HF, El Kommos ME (2002) J Pharm Biomed Anal 27:607–614
Mohamed NAL, Kuroda Y, Shibukawa A, Nakagawa T, El Gizawy S, Askal HF, El Kommos ME (2000) J Chromatogr A 875:447–453
Mohamed NAL, Kuroda Y, Shibukawa A, Nakagawa T, El Gizawy S, Askal HF, El Kommos ME (1999) J Pharm Biomed Anal 21:1037–1043
Hebb AR, Godwin TF, Gunton RW (1968) Can Med Assoc J 98:246–251
Hansson L, Malmerona R, Olander R, Rosenhall L, Westerlund A, Aberg H, Hood B (1972) Klein Wschr 50:364–369
Harrison DC, Griffin JR, Fiene TJ (1965) N Engl J Med 273:410–415
Henry JA, Dunlop AW, Mitchell SN, Turner P, Adams P (1981) J Pharm Pharmacol 33:179–182
Plumb RS, Potts WB III, Rainville PD, Alden PG, Shave DH, Baynham G, Mazzeo JR (2008) Rapid Commun Mass Spectrom 22:2139–2152
Barklay M (1972) In: Nelson GJ (ed) Blood Lipids and lipoproteins: quantitation, composition, and metabolism. Wiley, New York, pp 587–603
Wasan KM, Cassidy SM (1998) J Pharm Sci 87:411–424
Harmony JAK, Aleson AL, McCarthy BM (1986) In: Scanu AM, Spector AA (eds) Biochemistry and biology of plasma lipoproteins. Marcel Dekker, New York, pp 403–430
Mbewu AD, Durrington PN (1990) Atherosclerosis 85:1–14
Durrington PN (1989) In: Durrington PN (ed) Lipoproteins and lipids. Wright, London, pp 255–277
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 1129–1138
Skipski VR (1972) In: Nelson GJ (ed) Blood Lipids and lipoproteins quantitation, composition, and metabolism. Wiley, New York, pp 471–583
Kwong TC (1985) Clin Chim Acta 151:193–216
Chen S, Sobansky M, Hage DS (2010) Anal Biochem 397:107–114
Kim HS, Wainer IW (2008) J Chromatogr B 870:22–26
Hollósy F, Valkó K, Hersey A, Nunhuck S, Kéri G, Bevan C (2006) J Med Chem 49:6958–6971
Buchholz L, Cai CH, Andress L, Cleton A, Brodfuehrer J, Cohen L (2002) Eur J Pharm Sci 15:209–215
Loun B, Hage DS (1994) Anal Chem 66:3814–3822
Hage DS, Chen J (2006) In: Hage DS (ed) Handbook of affinity chromatography. CRC/Taylor & Francis, New York, pp 595–628
Tweed S, Loun B, Hage DS (1997) Anal Chem 69:4790–4798
Mallik R, Xuan H, Hage DS (2007) J Chromatogr A 1149:294–304
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 34:1311–1321
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This work was supported by the National Institute of Health under grant R01 GM044931 and was performed in facilities renovated under grant RR015468-01.
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Sobansky, M.R., Hage, D.S. Analysis of drug interactions with very low density lipoprotein by high-performance affinity chromatography. Anal Bioanal Chem 406, 6203–6211 (2014). https://doi.org/10.1007/s00216-014-8081-4
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DOI: https://doi.org/10.1007/s00216-014-8081-4