Development and validation of a stability- indicating RP-HPLC method for determination of aripiprazole and its degradation products

Abstract

The goal of this study was the optimization of chromatographic conditions and validation of the isocratic RP-HPLC method for monitoring the stability of aripiprazole, identification and quantitative analysis of aripiprazole and its degradation products in tablets. In addition, robustness was tested by applying the methodology of experimental design. The forced degradation study of aripiprazole was conducted in accordance with the ICH guidelines. The stability of the active pharmaceutical substance was tested under the conditions of hydrolysis in acidic, neutral and basic environments, thermal degradation, oxidation and photolysis. The active pharmaceutical ingredient was degraded under oxidation conditions, and the identity of the resulting degradation product, N-oxide, was confirmed. Under the other conditions tested, the active pharmaceutical substance was found to be stable. The developed method RP-HPLC allowed the separation of degradation products and aripiprazole and was defined as a stability-indicating method. The proposed method was validated for qualitative and quantitative analysis of aripiprazole and its degradation products. Accordingly, selectivity, linearity, precision, accuracy, limit of detection, limit of quantification, and robustness of the method were tested. The Box-Behnken experimental design was used in robustness testing.

Cilj rada bio je optimizacija hromatografskih uslova i validacija izokratske HPLC metode za praćenje stabilnosti aripiprazola, identifikacija i kvantitativna analiza aripiprazola i njegovih degradacionih proizvoda u tabletama, kao i ispitivanje robusnosti predložene analitičke metode primenom eksperimentalnog dizajna. Studija forsirane degradacije aktivne farmaceutske supstance aripiprazola sprovedena je u skladu sa ICH smernicama. Ispitivana je stabilnost aktivne supstance u uslovima hidrolize u kiseloj, neutralnoj i baznoj sredini, termalne degradacije, oksidacije i fotolize. Aktivna supstanca je pokazala degradaciju u uslovima oksidacije, pri čemu je potvrđen identitet nastalog proizvoda, N-oksida, Pri ostalim ispitivanim uslovima, aktivna farmaceutska supstanca je pokazala stabilnost. Kako je predložena RP-HPLC metoda omogućila efikasno razdvajanje degradacionih proizvoda i aripiprazola, definisana je kao metoda za praćenje stabilnosti farmaceutskog proizvoda. Sprovedena je validacija predložene metode za istovremenu identifikaciju i kvantifikaciju aripiprazola i njegovih degradacionih proizvoda. Tom prilikom su ispitani selektivnost, linearnost, preciznost, tačnost, limit detekcije i limit kvantifikacije, a primenom Box- Behnkenovog eksperimentalnog dizajna ispitana je i robusnost metode.