Chromatography of 3-hydroxypyridin-4-ones: novel orally active iron chelators

Abstract

Thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) of 3-hydroxypyridin-4-ones has been investigated. These novel orally active iron chelators display extremely poor chromatographic behaviour on conventional bonded-silica phases. This poor chromatography in HPLC is characterised by non-symmetrical, often multiple peaks, and in TLC by streaking. This appears to be due to interaction of the compounds with saturable free silanol groups and residual metal impurities on the bonded silica phases. This problem in HPLC can partially be solved by mobile phase manipulations (e.g. addition of the analyte to the mobile phase, 5 mg/l). TLC also improves dramatically when analyte is added to the solvent system (5 mg/50 ml). However in HPLC, due to poor selectivity, a better solution is the use of non-silica-based columns of columns with high carbon loading. The recently developed material, porous graphitised carbon (PGC Hypercarb®), is in particular an excellent HPLC phase for the separation of a series of these hydroxypyridinone iron chelators. © 1990.