Ispitivanje stabilnosti anizomicina metodom tečne hromatografije sa tandem masenom spektrometrijom

Abstract

U cilju poboljšanja kvaliteta leka i unapređenja sigurnosti njegovog korišćenja, potrebno je praćenje stabilnosti i određivanje degradacionih proizvoda koji mogu nastati tokom proizvodnje, rukovanja ili čuvanja leka. Cilj ovog rada je ispitivanje stabilnosti i praćenje degradacije višefun-kcionalnog leka anizomicina. Stabilnost anizomicina je ispitivana sprovođenjem studija forsirane degradacije, koje obuhvataju ispitivanje osetljivosti leka na hidrolizu (kiselu, baznu i neutralnu), oksidaciju, svetlost (vidljivu i UV) i povišenu temperaturu, u skladu sa ICH (eng. International Conference on Harmonization) smernicama. Za praćenje degradacije leka i identifikaciju degradacionih prozvoda korišćena je metoda tečne hromatografije sa tandem masenom spek-trometrijom. Pokazano je da je anizomicin stabilan u prisustvu oksidacionog sredstva i svetlosti, umereno stabilan u kiseloj i neutralnoj sredini, jako nestabilan u baznoj sredini i termo-degradabilan. Deacetilanizomicin je identifikovan kao glavni proizvod degradacije anisomicina.

In order to improve the quality of a drug and its safety usage, it is necessary to monitor stability of a drug and to determine degradation products that may form during production, usage and storage. Aim of this work was to investigate stability and monitor degradation of the multifunctional drug anisomycin. Stability of anisomycin was studied by performing force degradation that includes investigation of susceptibility of the drug to hydrolysis (acidic, alkaline and neutral), oxidation, light (visible and UV) and temperature, in accordance with ICH (International Conference on Harmonization) guidelines. Liquid chromatography coupled to tandem mass spectrometry was used for investigation of the drug degradation and identification of the degradation products. It was shown that anisomycin was stable in the presence of oxidizing agent and light, moderately stable under acidic and neutral conditions, very unstable under alkaline conditions and thermodegradable. Deacetylanisomycin was identified as the principal degradation product of anisomycin.