High-Sensitivity LC-MS/MS Approach for Accurate Quantification of N-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.