Determination of unbound ticagrelor and its active metabolite (AR-C124910XX) in human plasma by equilibrium dialysis and LC-MS/MS

Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences

Volumn 879, Issue 23, 2011, Pages 2315-2322

  Sillén, Henrik ^a   Cook, Melanie ^b   Davis, Patty ^c  

^a ASTRAZENECA R AND D   (Sweden)

^b York Bioanalytical Solutions   (United Kingdom)

^c ASTRAZENECA   (United Kingdom)

Author keywords

AZD6140; Equilibrium dialysis; P2Y 12 receptor inhibitor; Platelets; Ticagrelor; Unbound concentration

Indexed keywords

AZD6140; EQUILIBRIUM DIALYSIS; P2Y 12 RECEPTOR INHIBITOR; TICAGRELOR; UNBOUND CONCENTRATION;

BIOCHEMISTRY; DIALYSIS; LIQUID CHROMATOGRAPHY; METABOLISM; METABOLITES; PLASMA (HUMAN); PLATELETS; PROTEINS;

PLASMAS;

AR C124910XX; DRUG METABOLITE; PHOSPHATE BUFFERED SALINE; TICAGRELOR; UNCLASSIFIED DRUG;

ARTICLE; BLOOD SAMPLING; CONTROLLED STUDY; DIALYSATE LEVEL; DRUG BLOOD LEVEL; DRUG DETERMINATION; DRUG PROTEIN BINDING; EQUILIBRIUM DIALYSIS; HUMAN; LIMIT OF QUANTITATION; LIQUID CHROMATOGRAPHY; PRIORITY JOURNAL; TANDEM MASS SPECTROMETRY; VALIDATION PROCESS;

ADENOSINE; CHROMATOGRAPHY, LIQUID; DIALYSIS; HUMANS; PROTEIN BINDING; PURINERGIC P2Y RECEPTOR ANTAGONISTS; TANDEM MASS SPECTROMETRY;

EID: 79960562681     PISSN: 15700232     EISSN: 1873376X     Source Type: Journal    
DOI: 10.1016/j.jchromb.2011.06.023     Document Type: Article

References (27)

1. Springthorpe B., Bailey A., Barton P., Birkinshaw T.N., Bonnert R.V., Brown R.C., Chapman D., Dixon J., Guile S.D., Humphries R.G., Hunt S.F., Ince F., Ingall A.H., Kirk I.P., Leeson P.D., Leff P., Lewis R.J., Martin B.P., McGinnity D.F., Mortimore M.P., Paine S.W., Pairaudeau G., Patel A., Rigby A.J., Riley R.J., Teobald B.J., Tomlinson W., Webborn P.J., Willis P.A. Bioorg. Med. Chem. Lett. 2007, 17:6013.
2. Husted S., van Giezen J.J.J. Cardiovasc. Ther. 2009, 27:259.
3. van Giezen J.J.J. Eur. Heart J. 2008, 10(suppl. D):D23.
4. Butler K., Teng R. Brit. J. Clin. Pharmacol. 2010, 70:65.
5. Teng R., Butler K. Eur. J. Clin. Pharmacol. 2010, 66:487.
6. European Medicines Agency. EPAR summary for the public, Ticagrelor, October 2010. Available from URL: (accessed 16.03.11). http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/002303/WC500100562.pdf.
7. Husted S., Emanuelsson H., Heptinstall S., Sandset P.M., Wickens M., Peters G. Eur. Heart J. 2006, 27:1038.
8. Cannon C.P., Husted S., Harrington R.A., Scirica B.M., Emanuelsson H., Peters G., Storey R.F. J. Am. Coll. Cardiol. 2007, 50:1844. DISPERSE-2 Investigators.
9. James S., Åkerblom A., Cannon C., Emanuelsson H., Husted S., Katus H., Skene A., Steg P.G., Storey R.F., Harrington R., Becker R., Wallentin L. Am. Heart J. 2009, 157:599.
10. Wallentin L., Becker R.C., Budaj A., Cannon C.P., Emanuelsson H., Held C., Horrow J., Husted S., James S., Katus H., Mahaffey K.W., Scirica B.M., Skene A., Steg P.G., Storey R.F. N. Engl. J. Med. 2009, 361:1045. R.A. Harrington for the PLATO Investigators.
11. Mullangi R., Srinivas N.R. Biomed. Chromatogr. 2009, 23:26.
12. Mackichan J.J. Applied Pharmacokinetics and Pharmacodynamics: Principles of Therapeutic Drug Monitoring 2006, 82. Lippincott Williams & Wilkins. M.E. Burton, L.M. Shaw, .J. Schentag, W.E. Evans (Eds.).
13. Acharya M.R., Sparreboom A., Sausville E.A., Conley B.A., Doroshow J.H., Venitz J., Figg W.D. Cancer Chemother. Pharmacol. 2006, 57:275.
14. Wright J.D., Boudinot F.D., Ujhelyi M.R. Clin. Pharmacokinet. 1996, 30:445.
15. Bowers W.F., Fulton S., Thompson J. J. Clin. Pharmacokinet. 1984, 9(suppl. 1):49.
16. Oellerich M., Müller-Vahl H. Clin. Pharmacokinet. 1984, 9(suppl. 1):61.
17. Brouwer E., Verweij J., De Bruijn P., Loos W.J., Pillay M., Buijs D., Sparreboom A. Drug Metab. Dispos. 2000, 28:1141.
18. Johnsson A., Björk H., Schütz A., Skärby T. Cancer Chemother. Pharmacol. 1998, 41:248.
19. Shibukawa A., Kuroda Y., Nakagawa T. J. Pharm. Biomed. Anal. 1999, 18:1047.
20. Oravcová J., Böhs B., Lindner W. J. Chromatogr. B: Biomed. Appl. 1996, 677:1.
21. Fan C., Tisdale J.E., Ujhelyi M.R., Chow M.S. Clin. Pharm. 1993, 12:917.
22. Sillén H., Cook M., Davis P. J. Chromatogr. B 2010, 878:2299.
23. de Smet R., van Kaer J., Liebich H., Lesaffer G., Verstraete A., Dhondt A., Duym P., Lameire N., Vanholder R. Clin. Chem. 2001, 47:901.
24. Nilsson L.B., Schmidt S. J. Pharm. Biomed. Anal. 2001, 24:921.
25. US FDA, Guidance for Industry Bioanalytical Method Validation, May 2001. Available at: (accessed 22.02.11). http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070107.pdf.
26. K. Butler, R. Teng, J. Clin. Pharmacol., 6 October 2010 (Epub ahead of print).
27. Herforth C., Stone J.A., Jayewardene A.L., Blaschke T.F., Fang F., Motoya T., Aweeka F.T. Eur. J. Pharm. Sci. 2002, 15:185.