Development and validation of ultra-performance liquid chromatography method for the analysis of cinnarizine degradation products

Abstract

Kemijska stabilnost aktivnih farmaceutskih sastojaka utječe na sigurnost i učinkovitost lijekova. U sklopu ovog diplomskog rada razvijena je, a zatim i validirana stabilitetno-indikativna metoda tekućinske kromatografije ultravisoke djelotvornosti uz detektor s diodnim nizom za praćenje kemijske stabilnosti cinarizina. Kako bi se razvila prikladna stabilitetno-indikativna analitička metoda najprije je provedena prisilna razgradnja na uzorcima cinarizina. Provedena je razgradnja pod utjecajem hidrolitičkih uvjeta (u neutralnom, kiselom i bazičnom mediju) pri temperaturi od 80 °C, razgradnja pod utjecajem oksidativnih uvjeta te fotolitička razgradnja cinarizina u otopini pri sobnoj temperaturi. Strukturna karakterizacija razgradnih produkata provedena je korištenjem spregnutog sustava tekućinska kromatografija ultravisoke djelotovornosti – spektrometrija masa visokog razlučivanja, uz eksperimente tandemne spektrometrije masa na ionima od interesa pri različitim vrijednostima kolizijskih potencijala.The chemical stability of active pharmaceutical ingredients affects the safety and effectiveness of drugs. As part of this thesis, a stability-indicative method of ultra-high efficiency liquid chromatography with a diode array detector for monitoring the chemical stability of cinnarizine was developed and then validated. To develop a suitable stability-indicative analytical method, forced degradation was performed on cinnarizine samples. Degradation under the influence of hydrolytic conditions (in neutral, acidic, and basic media) at a temperature of 80 °C, degradation under the influence of oxidative conditions and photolytic degradation of cinnarizine in solution at room temperature were carried out. Structural characterization of degradation products was carried out using a coupled system of ultra-high performance liquid chromatography – high resolution mass spectrometry, with tandem mass spectrometry experiments on ions of interest at different values of collision potentials