HPLC study on stability of pyridoxal isonicotinoyl hydrazone

Abstract

Biocompatible iron chelators are currently under extensive investigation as promising drug candidates. Pyridoxal isonicotinoyl hydrazone (PIH) is a lead compound of the aroylhydrazone group of novel iron chelating agents. In this study, the precise and accurate HPLC analytical methods were used for the stability evaluation of water-soluble PIH salt (PIH·2HCl) in aqueous media of different pH (2.0, 3.9, 7.0, 9.0 and 12.0) as well as in two selected pharmaceutical co-solvents at both laboratory and elevated (40 °C) temperatures. The susceptibility of PIH·2HCl to oxidative decomposition was studied in the solutions of hydrogen peroxide (3 and 30%). Furthermore, the solid substance of PIH·2HCl was exposed to UV, dry and wet heat. Our experiments revealed that PIH was considerably sensitive to hydrolytic decomposition in aqueous media, resulting in the splitting of the hydrazone bond. The elevated temperature significantly accelerated the hydrolytic reaction. The lowest rate of hydrolysis of PIH was observed in the phosphate buffer of pH 7.0 and in the pharmaceutical co-solvents (30% PEG-300 and 10% Cremophor EL). No special degradation products were detected in the samples exposed to either hydrogen peroxide or co-solvents. The solid substance of PIH·2HCl was stable when exposed to UV, dry or wet heat for 33 h.