engleski

Development of ultra performance liquid chromatographic method for the analysis of Dasatinib degradation products

Dasatinib is active pharmaceutical ingredient used to treat a certain type of chronic myeloid leukemia (CML). Impurities in pharmaceutical product are the unwanted chemical compounds that remain within the active pharmaceutical ingredient (API), or are formed during production process or by degradation of API. The presence of these unwanted chemical compounds even at small concentrations may influence the efficacy and safety of the pharmaceutical products. Degradation products can be potentially genotoxic, mutagenic or carcinogenic, thus needing constant monitoring and impurity profiling. In this study efficient ultra‐high performance liquid chromatography (UHPLC) method for determination of impurities and degradation products of Dasatinib was developed. DryLab, commercial software for UHPLC method development, was used to determine the optimal conditions for UHPLC separation like temperature, time of gradient elution and composition of the mobile phase. DryLab enabled prediction of retention times in dependence of method parameters from 12 preliminary experiments. The obtained optimal method conditions were checked and mathematical model was confirmed by experiments. Dasatinib was subjected to forced degradation under the following conditions: hydrolysis, photolysis, oxidation, dry and wet heat, all in accordance with the International Conference on Harmonization [1, 2]. Degradation products were analyzed by LC‐MS/MS system. Based on the MS and MS/MS spectra, the structures of degradation products, as well as fragmentation schemes were proposed [3].

Dasatinib ; UPLC ; degradation products

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