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Open AccessArticle

Pharmacokinetic Profiling and Simultaneous Determination of Thiopurine Immunosuppressants and Folic Acid by Chromatographic Methods

1
Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia
2
Clinical Hospital Center Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia
3
Public Health Brčko DC, R. Dž. Čauševića 1, 76100 Brčko DC, Bosnia and Herzegovina
*
Author to whom correspondence should be addressed.
Molecules 2019, 24(19), 3469; https://doi.org/10.3390/molecules24193469
Received: 29 August 2019 / Revised: 20 September 2019 / Accepted: 22 September 2019 / Published: 24 September 2019
(This article belongs to the Special Issue Recent Trends in Pharmaceutical Analytical Chemistry)
With the increase in the number of medicines patients have to take, there has been a rapid rise of fixed-dose combinations (FDCs) in the last two decades. Prior to FDC development, pharmacokinetic properties of active pharmaceutical ingredients (APIs) have to be evaluated, as well as methods for their determination developed. So as to increase patient compliance in inflammatory bowel disease, three novel FDCs of thiopurine immunosuppressants and folic acid are proposed; physico-chemical and pharmacokinetic properties such as hydrophobicity, lipophilicity and plasma protein binding of all APIs are evaluated. Moreover, experimental results of different properties are compared to those computed by various on-line prediction platforms so as to evaluate the viability of the in silico approach. A simultaneous method for their determination is developed, optimized, validated and applied to commercial tablet formulations. The method has shown to be fast, selective, accurate and precise, showing potential for reliable determination of API content in proposed FDCs during its development. View Full-Text
Keywords: inflammatory bowel disease; fixed-dose combination; biomimetic chromatography; thiopurine immunosuppressants; folic acid inflammatory bowel disease; fixed-dose combination; biomimetic chromatography; thiopurine immunosuppressants; folic acid
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MDPI and ACS Style

Brusač, E.; Jeličić, M.-L.; Amidžić Klarić, D.; Nigović, B.; Turk, N.; Klarić, I.; Mornar, A. Pharmacokinetic Profiling and Simultaneous Determination of Thiopurine Immunosuppressants and Folic Acid by Chromatographic Methods. Molecules 2019, 24, 3469.

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