HPLC study on stability of pyridoxal isonicotinoyl hydrazone.
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 x 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 degrees C) temperatures. The susceptibility of PIH x 2HCl to oxidative decomposition was studied in the solutions of hydrogen peroxide (3 and 30%). Furthermore, the solid substance of PIH x 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 x 2HCl was stable when exposed to UV, dry or wet heat for 33 h.
Kovaríková
P
P
Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. petra.kovarikova@faf.cuni.cz
Mokrý
M
M
Klimes
J
J
Vávrová
K
K
D002138:Calibration; D002623:Chemistry Techniques, Analytical; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002845:Chromatography; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D006835:Hydrazones / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007501:Iron / Q000737:chemistry; D007502:Iron Chelating Agents / Q000494:pharmacology; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D010100:Oxygen / Q000737:chemistry; D011730:Pyridoxal / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013696:Temperature; D013997:Time Factors; D014466:Ultraviolet Rays
D006835:Hydrazones; D007502:Iron Chelating Agents; D012997:Solvents; D011730:Pyridoxal; C021079:pyridoxal isonicotinoyl hydrazone; D006861:Hydrogen Peroxide; D007501:Iron; D010100:Oxygen; D007538:Isoniazid