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Analytical evaluation of novel drug candidates from the group of iron chelators using HPLC II.
Tomalová, Kateřina ; Kovaříková, Petra (advisor) ; Kučera, Radim (referee)
High performance liquid chromatography (HPLC) has a dominant position among the modern techniques in both the qualitative and quantitative drugs analysis. After adequate sample preparation it is also commonly used for the determination of drugs and metabolites in biological material. This study is focused on the development and validation of a chromatographic method suitable for the analysis of 2',4'-dihydroxyacetophenon isonicotinoyl hydrazone (DHAP-INH) - a novel biocompatible iron chelator, and its application for stability evaluation of this drug candidate in rabbit plasma in vitro. DHAP-INH is among newly synthesized salicylaldehyde isonicotinoyl hydrazone (SIH) analogues, which were prepared to improve compound stability in plasma and thus make pharmacokinetic profile of aroylhydrazones more favorable. Sufficient separation of DHAP-INH, its synthetic precursors/degradation products (2,4-dihydroxyacetophenon and isoniazide) and internal standard (SIH) was achieved on LiChrospher 100, RP-18 column (250 mm × 4,6 mm ID, 5 mm) employing a mobile phase composed of a mixture of phosphate buffer (0.01 M NaH2PO4.2H2O; 2 mM EDTA; pH 6,0) and methanol in a ratio of 54:46 (v/v). UV detection was performed at 254 and 326 nm. Different organic solvents were tested as precipitation agents, however...
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