Characterization of Plasma Protein Binding and the Effect of the Vehicle of Docetaxel Formulations

Maripaz Márquez, Liliana Quintanar, Gilberto Castañeda-Hernández


In this study we provide evidence of the alpha-1-acid glycoprotein (AAG) binding to Docetaxel as a key assay to evaluate formulations from different manufactures. The comparison of generics to the innovator is an active field in Pharmaceutics. While quality control tests are based on the evaluation of the active drug, our results show protein binding and excipients (Polysorbate 80) also play a critical role. We designed an assay by electronic absorption spectroscopy to evaluate the Docetaxel binding to AAG and the influence of Polysorbate 80. We evaluated Docetaxel generics from India and Latin America, our results show some generics of Docetaxel do not match with the innovator. The assay here developed is a feasible and easy access technique that could be implemented as a quick scan of quality control of Docetaxel generics available worldwide.


Docetaxel; alpha-1-acid glycoprotein (AAG); Polysorbate 80; generics; protein binging.

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Baker S.D.; Li J.; ten Tije A.J.; Figg W.D.; Graveland W.; Verweij J.; Sparreboom A. Clin Pharmacol Ther. 2005, 77, 43-53.

Vial J.; Cohen M.; Sassiat P.; Thiébaut D. Curr Med Res Opin. 2008, 24, 2019-2033. DOI:

Ng S.S., Figg W.D., Sparreboom A. Cancer Res. 2004, 64, 821-824.

Jill M Kolesar. J Oncol Pharm Practice. 2000, 6, 43-49.

Urien S.; Barré J.; Morin C.; Paccaly A.; Montay G.; Tillement J.P. Invest New Drugs. 1996, 14, 147-151.

Sparreboom A.; Zhao M.; Brahmer J.R.; Verweij J.; Baker S.D. J Chromatogr B Analyt Technol Biomed Life Sci. 2002, 773, 183-190.

Carstens M.G.; de Jong P.H.; van Nostrum C.F.; Kemmink J.; Verrijk R.; de Leede L.G.; Crommelin D.J.; Hennink W.E. Eur J Pharm Biopharm. 2008, 68, 596-606.

Vasu Dev R.; Moses Babu J.; Vyas K.; Sai Ram P.; Ramachandra P.; Sekhar N.M.; Mohan Reddy D.N.; Srinivasa Rao N. J Pharm Biomed Anal. 2006, 40, 614-622.

Datamonitor. 2010 [cited 2013; Available from: o n e d _ t o _ h e l p _ o ff s e t _ t a x o t e r e _ d e c l i n e ? p r o d u c -tid=35244E18-A4E1-4435-8797-DEFE94A569BE.

EMEA. Europena Medicines Agency Evaluation of Medicines for Human. Assessment Report for Docetaxel Teva. .Procedure No.EMEA/H/C/1107.2010. 2010 [cited 2013; Available from: PDF.

Malleswara Reddy, A., et al., Evaluation of the pharmaceutical quality of docetaxel injection using new stability indicating chromatographic methods for assay and impurities. Sci Pharm, 2010. 78(2): p. 215-31.

Loos, W.J., et al., Clinical pharmacokinetics of unbound docetaxel: Role of polysorbate 80 and serum proteins. Clinical Pharmacology & Therapeutics, 2003. 74(4): p. 364-371.

Aizawa, H., Morphology of polysorbate 80 (Tween 80) micelles in aqueous 1,4-dioxane solutions. . J Appl Crystallogr, 2009. 42: p. 592-596.

Croy, S.R. and G.S. Kwon, Polysorbate 80 and Cremophor EL micelles deaggregate and solubilize nystatin at the core-corona interface. J Pharm Sci, 2005. 94(11): p. 2345-54.

Engels, F.K., R.A. Mathot, and J. Verweij, Alternative drug formulations of docetaxel: a review. Anticancer Drugs, 2007. 18(2): p. 95-103.

Acharya, M.R., et al., Determination of fraction unbound docetaxel using microequilibrium dialysis. Anal Biochem, 2004. 331(1): p. 192-4.

Goodman and Gilman, eds. Las bases farmacológicas de la terapéutica. 11 ed., ed. M.G. Hill. 2007.

Ascoli, G.A., C. Bertucci, and P. Salvadori, Ligand binding to a human serum albumin stationary phase: Use of same-drug competition to discriminate pharmacologically relevant interactions. Biomedical Chromatography, 1998. 12(5): p. 248-254.

Sugio, S., et al., Crystal structure of human serum albumin at 2.5 angstrom resolution. Protein Engineering, 1999. 12(6): p. 439-446.

Otagiri, M. and V.T.G. Chuang, Pharmaceutically Important Preand Posttranslational Modifications on Human Serum Albumin. Biological & Pharmaceutical Bulletin, 2009. 32(4): p. 527-534.

Otosu, T., E. Nishimoto, and S. Yamashita, Multiple conformational state of human serum albumin around single tryptophan residue at various pH revealed by time-resolved fluorescence spectroscopy. J Biochem, 2010. 147(2): p. 191-200.

Otagiri, M., A molecular functional study on the interactions of drugs with plasma proteins. Drug Metab Pharmacokinet, 2005. 20(5): p. 309-23.

Ghuman, J., et al., Structural basis of the drug-binding specificity of human serum albumin. J Mol Biol, 2005. 353(1): p. 38-52.

Schonfeld, D.L., et al., The 1.8-A crystal structure of alpha1-acid glycoprotein (Orosomucoid) solved by UV RIP reveals the broad drug-binding activity of this human plasma lipocalin. J Mol Biol, 2008. 384(2): p. 393-405.

Kawasaki, T., J. Koyama, and Yamashin.I, Isolation and Characterization of Alpha1-Acid Glycoprotein from Rat Serum. Journal of Biochemistry, 1966. 60(5): p. 554-&.

Fournier, T., N. Medjoubi-N, and D. Porquet, Alpha-1-acid glycoprotein. Biochimica Et Biophysica Acta-Protein Structure and Molecular Enzymology, 2000. 1482(1-2): p. 157-171.

Routledge, P.A., The Plasma-Protein Binding of Basic Drugs. British Journal of Clinical Pharmacology, 1986. 22(5): p. 499-506.

Williams, J.P., et al., alpha(1)-acid glycoprotein reduces local and remote injuries after intestinal ischemia in the rat. American Journal of Physiology-Gastrointestinal and Liver Physiology, 1997. 273(5): p. G1031-G1035.

ten Tije, A.J., et al., Pharmacological effects of formulation vehicles: implications for cancer chemotherapy. Clin Pharmacokinet, 2003. 42(7): p. 665-85.

Loos, W.J., et al., Influence of polysorbate 80 on unbound fractions of anticancer agents. European Journal of Cancer, 2002. 38: p. S38-S38.

Cheng, H.X., et al., Interaction of the docetaxel with human serum albumin using optical spectroscopy methods. Journal of Luminescence, 2009. 129(10): p. 1196-1203.

Márquez M., Quintanar L., and C.-H. G. Rev Mex Cienc Farm 2013. 44 (1) p. 45-51.



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Journal of the Mexican Chemical Society (J. Mex. Chem. Soc.) Vol 62, No 2 (2018). Quarterly publication (April-June). Edited and distributed by Sociedad Química de México, A.C. Barranca del Muerto 26, Col. Crédito Constructor, Del. Benito Juárez, C.P. 03940, Mexico City. Phone: +5255 56626837; +5255 56626823 Contact: Editor-in-Chief: Ignacio González-Martínez. Indexed Journal. Certificate of reserved rights for recurrent publications under digital distribution granted by the Instituto Nacional del Derecho de Autor (INDAUTOR): 04-2018-091118040000-203. Certificate of lawful title and content: Under procedure. ISSN-e granted by the Instituto Nacional del Derecho de Autor (INDAUTOR): 2594-0317. ISSN granted by the Instituto Nacional del Derecho de Autor (INDAUTOR): 1870-249X. Postal registration of printed matter deposited by editors or agents granted by SEPOMEX: IM09-0312 Copyright © Sociedad Química de México, A.C. Total or partial reproduction is prohibited without written permission of the right holder. The Figures/schemes quality and the general contents of this publication are full responsibility of the authors. Updated December 12th, 2018 by Adriana Vázquez (editorial assistant, e-mail:, J. Mex. Chem. Soc., Sociedad Química de México, A.C.