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Development and validation of stability indicative UHPLC method for determination of crizotinib and its degradation products

In addition to the pharmaceutically active substance, it is also essential to know about the impurities present in the drug, resulting from its production or degradation. According to the ICH guidelines, impurities are classified as organic impurities, inorganic impurities and residual solvents. Organic impurities include products originated by degradation of active pharmaceutical ingredient (API) under the influence of temperature, light, pH change, etc [1]. Various studies have shown that new formed degradation impurities may have different toxic effects and impacts on safety and efficacy of the applied drug. For this purpose, forced degradation studies, also defined according to the ICH guidelines, are conducted exposing the new drug to various stress conditions (hydrolysis: acid and basic, oxidation, photolysis, humidity, temperature...) in order to develop a stable- indicative method and define the degradation pathways for a new active substance. According to a literature review, only a few methods for the analysis of crizotinib in pharmaceutical dosage have been developed. Crizotinib is a pharmaceutical used in the treatment of lung cancer as a tyrosine kinase receptor inhibitor. Therefore, the aim of this research was to develop and validate the new RP-UHPLC-DAD selective method for the determination of crizotinib in the presence of the resulting degradation products. Its stability was tested by forced degradation studies in acidic, basic and oxidizing conditions. The major degradation products were subsequently identified and characterized by liquid chromatography coupled to a mass spectrometer as a detector.

Crizotinib ; Forced degradation ; Stability indicating study ; Ultra high performance liquid chromatography ; Degradation products

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