HPLC-DAD and MS/MS analysis of novel drug candidates from the group of aromatic hydrazones revealing the presence of geometric isomers.
Salicylaldehyde isonicotinoyl hydrazone (SIH) is an iron-chelating aromatic hydrazone with promising pharmacological properties. However, it suffers from relatively short biological half-life. Hence, two novel derivates of SIH, HAP-INH and HPP-INH were synthesized in order to overcome this pharmacokinetic drawback. The aim of the present study was to employ HPLC-DAD and HPLC-MS/MS methods to investigate the identity of the putative impurities of these newly prepared substances, which are being formed in aqueous environment. At first, it was shown that their retention times as well as UV spectra did not correspond to any expected synthetic precursor, by-product or degradation product. HPLC-DAD analysis confirmed purity of peaks and revealed close but not identical UV spectra of putative impurities and corresponding hydrazones. The subsequent HPLC-MS/MS analyses using ESI and the ion trap mass analyzer showed the identical molecular ions (in both modes) as well as their fragmentation, which implicated presence of geometric isomers. This suggestion was further supported by the NMR analyses. Since the Z/E isomers can have different biological activities, results of this study might be of great importance for further development of the aroylhydrazones as novel drug candidates as well as from the theoretical point of view.
Kovaríková
Petra
P
Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic. petra.kovarikova@faf.cuni.cz
Vávrová
Katerina
K
Tomalová
Katerina
K
Schöngut
Michal
M
Hrusková
Katerina
K
Hasková
Pavlína
P
Klimes
Jirí
J
D000447:Aldehydes / Q000032:analysis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006835:Hydrazones / Q000032:analysis* / Q000737:chemistry; D007536:Isomerism; D013058:Mass Spectrometry / Q000379:methods*
D000447:Aldehydes; D006835:Hydrazones; C413684:salicylaldehyde isonicotinoyl hydrazone