engleski

Analysis of Nepafenac degradation-related impurities by two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry(2D-LC-QTOF MS)

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. Different scientific researches showed that degradation products can be potentially genotoxic, mutagenic or carcinogenic, thus needing constant monitoring and impurity profiling. Techniques such as LC/MS/MS are widely used for impurity identification in pharmaceutical industries due to their high sensitivity, selectivity, and speed of analysis. Coupling high pressure liquid chromatography (HPLC) system with quadrupole time-of-flight (Q-TOF) mass spectrometry enables accurate mass measurement of both precursor and fragment ions ; however this technique is limited to the usage of volatile buffers. Additional time is required to develop an equivalent HPLC method with MS compatible mobile phase. Furthermore, it may add additional challenges and uncertainty if the impurity elution order is changed with the newly developed MS-compatible LC method. This limitation can be effectively resolved with a heart-cut approach employing two reversed phase LC conditions. Heart-cutting 2D-LC transfers fractions of interest from first to second dimension ensuring the best separation at the critical parts of the chromatogram. In order to investigate the stability of nonsteroidal anti-inflammatory drug (NSAID) Nepafenac, the selected model drug was subjected to forced degradation under different stress conditions such as oxidation, acid and base hydrolysis (Runje et al., 2016). The aim of this stability study was to propose the structure of unknown peaks and demonstrate the application of two-dimensional chromatography coupled with quadrupole time-of-flight (Q-TOF) mass detector for impurity profiling purposes. Major degradation impurities were determined and the peak purity was determined by usage of selected MS detector.

nepafenac; degradation related impurities; 2D-LC-QTOF MS

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