High‐Sensitivity LC‐MS/MS Approach for Accurate Quantification of <i>N</i>‐Nitroso Duloxetine in Duloxetine Pharmaceutical Formulations

The high-sensitivity analytical method for the detection of N-nitroso duloxetine, which can be carcinogenic in duloxetine medication products, was successfully developed by applying liquid chromatography-tandem mass spectrometry. Chromatographic separation was achieved by using liquid chromatography-mass spectrometry was carried out by employing an Agilent Zorbax Eclipse Plus C18, 4.6 × 150 mm, 5-μm column. The gradient elution mode was used to operate the mobile phase, which consisted of Phase A, which was a solution of 0.1% ammonia and 0.1% formic acid in water, and Phase B, 100% methanol. This approach overcame duloxetine challenges. Tandem mass spectrometric detection with positive electro spray ionization in MRM mode then found N-nitroso duloxetine. Quality control involves verifying the method for precision, specificity, linearity, accuracy, and robustness, following ICH and USP criteria <1225> to ensure suitability and consistent results. On the other hand, the correlation coefficient (r) was more than 1.000, the mean impurity recovery ranged from 100.5% to 102.4%, and the relative standard deviation (RSD) values (n = 6) ranged from 1.54% to 2.6% over the ranges of LOQ-150%. This work seeks to simplify risk assessment for N-nitroso duloxetine in duloxetine pharmaceutical formulations by providing a fast and reliable quantitative LC-MS/MS analytical method.