Development And Validation Of N-Nitroso Atomoxetine Impurity (Ndsri) Determination Method In Atomoxetine Hydrochloride With Uflc-Ms/Ms (Esi).

Abstract

Now a day’s nitrosamine impurities major concern for the pharmaceutical industries due to the cancer-causing potential, they can impact on health risk, recall the products and withdrawals, process modification, financial and operational impact. Multiple regulatory authority requirements for Pharmaceuticals for Human Use has established guidelines for nitrosamine impurities, which classify them as a cohort of concern (CoC) and present potential genotoxic risks. Therefore, controlling these impurities at lower levels during the quantification process in active pharmaceutical ingredients (API) and products is crucial to ensure safe human consumption. This research paper presented a simple, fast, and trace-level quantification by LC-ESI-MS-MS analytical method for N-Nitroso atomoxetine (NDSRI) in atomoxetine hydrochloride with a LOQ of 0.02 ppm and LOD 0.006 ppm. Chromatographic separation is achieved using HPLC column Kromasil 100-5C8 (250 mm x 4.6 mm x 5µ) and mobile phase A 1mL formic acid in water and mobile phase B acetonitrile. Gradient mode with 0.8 ml/min using a total run time of 23 min. Multiple reaction monitoring (MRM) with Electron Spray Ionization (ESI) is used to identification and quantify NDSRI in a positive mode and validate regulatory guidelines. MS diverter valve to avoid MS contamination from API. Validated method is specific, linear in the range of 0.02 ppm – 0.27 ppm with regression coefficient >0.99, Accurate & Precise. A triplicate sample preparation is used to establish method recoveries, which are found to be satisfactory within the range of 70% to 130%. The N-Nitroso atomoxetine impurity in atomoxetine hydrochloride can be regularly detected using this method