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2014-06-23 - Colloque/Présentation - poster - Anglais - 1 page(s)

Hambye Stéphanie , Helvenstein Maxime, Vanden Eynde Jean-Jacques, Blankert Bertrand , "First UPLC-Fluo/PDA quantification method of Pentamidine and a new promising analogue in biological fluids" in Drug Analysis, Liège, Belgique, 2014

  • Codes CREF : Chimie analytique (DI1314), Pharmacocinétique (DI3431), Sciences pharmaceutiques (DI3400), Techniques séparatives (DI2729)
  • Unités de recherche UMONS : Analyse pharmaceutique (M130)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)

Abstract(s) :

(Anglais) Pentamidine (PTMD) isethionate is a well-known diamidine derivative currently used in different parasitic diseases such as Pneumocystis jirovecii Pneumonia or Human African Trypanosomiasis [1]. This compound recently gained a new interest as a potential therapeutic agent in myotonic dystrophy type 1 (DM1), an orphan neuromuscular disease. Because of the high toxicity and the poor bioavailability exhibited by this compound, several analogues were synthetized in University of Mons. Some of them are currently being assessed and promising results should soon be published concerning DM1. For the first time, a new Ultra High Performance Liquid Chromatograph (UPLC) procedure coupled to fluorescence or PDA detection was developed [3]. This method aimed to quantify PTMD and the analogue with the most promising toxicity and efficacy characteristics, in rat plasma and urine. An innovative μSPE (solid phase extraction) procedure using Oasis® WCX sorbent was selected and gave satisfying and reproducible results in terms of extraction yields. Acquity UPLC® HSS T3 analytical column was used for the chromatographic separation with a mobile phase gradient combining formic acid 0.1% (v/v) and acetonitrile (ACN) at a constant flow rate of 0.4 mL/min. Afterwards, the method was successfully validated using the accuracy profiles approach (β = 95%; acceptance limits = 15–20 %) with the lowest limit of quantification and the shortest time of analysis ever described. The validated ranges are: 2.88 to 287.52 ng/mL and 143.76 ng/mL to 1.72 μg/mL in rat plasma and urine for PTMD and 4.23 to 423.39 ng/mL and 211.69 ng/mL to 2.54 μg/mL in rat plasma and urine, for the analogue. Thanks to the new method developed, a pharmacokinetic (PK) study on rats was performed and permitted to compare PK parameters of PTMD and its studied analogue. References : [1] M. Sands, M.A. Kron and R.B. Brown, Rev. infect. Dis., 1985, 7(5), 625-633. [2] M.B. Warf, M. Nakamori, C.M. Matthys, C.A. Thornton, J.A. Berglund, PNAS, 2009,106,18551-18556.