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Time Resolved Fluorescence Spectroscopic Detection of the Anticoagulant Warfarin: A Sensor-based Method for Direct Detection in Blood-plasma
Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. (BBCL)
Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. (BBCL)ORCID iD: 0000-0002-7392-0591
FOI, Swedish Defence Research Agency. (CBRN Defence & Security)
FOI, Swedish Defence Research Agency. (CBRN Defence & Security)
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2010 (English)Conference paper, (Refereed)
Abstract [en]

Warfarin is a clinically important drug widely used in the treatment of thrombolic disorders such as myocardial infarction and stroke [1]. When administered, 99% of the drug present in blood is bound to the transport protein human serum albumin (HSA) [2]. On account of the fact that HSA demonstrates polymorphism and warfarin has a narrow therapeutic window, careful monitoring of the effect of drug-dosage must be performed. Currently, warfarin’s anticoagulant effect is measured by an indirect method in which the clotting time is measured and correlated to the amount of warfarin present. As current methods for self-monitoring are limited, the development of alternative robust and more sensitive methods is desirable.

Molecular imprinting is a technique for the preparation of synthetic polymeric receptors (MIPs) with selective recognition for predetermined analyte [3]. In this study [4], we have used a non-covalent MIP system with selectivity for warfarin. The HSA-like binding properties of this MIP was developed from previous attempts to develop polymers with HSA-like binding of warfarin [5].

In principle the fluorophoric nature of warfarin should allow for the fluorescence spectroscopy-based detection of the drug. Recent efforts by us [6-8], using a series of theoretical and spectroscopic studies, have highlighted the complex nature of warfarin. In particular, the medium dependent isomerization of this drug illustrates why spectroscopy-based methods for the direct detection of the drug has not been forthcoming. Results from these studies have been used to develop a method for the in situ detection of warfarin using time correlated single photon counting (TCSPC). The application of this method for the detection of warfarin in blood is highlighted.

References

  1. Landefeld, C.; Beyth, R. Am. J. Med. 1993, 95, 315-328.
  2. Yacobi, A.; Udall, J. A.; Levy, G. Clin. Pharmacol. Ther. 1976, 19, 552-558.
  3. Alexander, C.; Andersson, H. S.; Andersson, L. I.; Ansell, R. J.; Kirsch, N.; Nicholls, I. A.; O’Mahony, J.; Whitcombe, M. J. J. Mol. Recognit. 2006, 19, 106-180.
  4. Rosengren, A. M.; Karlsson, B. C. G.; Näslund, I.; Andersson, P. O.; Nicholls, I. A. 2010, Submitted.
  5. Karlsson, B. C. G.; Rosengren, A. M.; Näslund, I.; Andersson, P. O.; Nicholls, I. A. 2010, Submitted.
  6. Karlsson, B. C. G.; Rosengren, A. M.; Andersson, P. O.; Nicholls, I. A. J. Phys. Chem. B 2007, 111, 10520-10528.
  7. Karlsson, B. C. G.; Rosengren, A. M.; Andersson, P. O.; Nicholls, I. A. J. Phys. Chem. B 2009, 113, 7945-7949.
  8. Nicholls, I. A.; Karlsson, B. C. G., Rosengren, A. M. J. Mol. Recognit. 2010, in press.
Place, publisher, year, edition, pages
2010.
National Category
Organic Chemistry
Research subject
Natural Science, Organic Chemistry
Identifiers
URN: urn:nbn:se:lnu:diva-6707OAI: oai:DiVA.org:lnu-6707DiVA: diva2:329002
Conference
19:th Analytical days (Analysdagarna), Uppsala
Available from: 2010-07-07 Created: 2010-07-07 Last updated: 2016-11-11Bibliographically approved

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