High‐Sensitivity LC‐MS/MS Method for Precise Quantification of N‐Nitroso Sertraline in the Antidepressant Sertraline Drug Products

ABSTRACT The presence of N‐nitrosamine impurities in medications has prompted serious regulatory concerns since they may cause cancer. N‐Nitroso Sertraline is one of the impurities that can develop during the production and storage of sertraline medicinal products, and it is considered to be a significant impurity. Chromatographic separation was achieved by using Waters XBridge C 8, 4.6×150 mm, 3.5 µm. The gradient elution technique was employed for the mobile phase, comprising Phase A, a solution of 0.1% formic acid in water, and Phase B, a solution of 0.1% formic acid in methanol with a flow rate of 0.8 mL/min. This work introduces a liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) approach that is extremely sensitive and selective for accurately measuring the amount of N‐Nitroso Sertraline in sertraline pharmaceutical formulations. The approach showed a high degree of linearity across the concentration range of LOQ‐150%, with a correlation coefficient ( R 2 ) greater than 0.99. The limit of detection (LOD) and limit of quantification (LOQ) were determined to be 0.03% and 0.05%, which allows for the identification of N‐Nitroso Sertraline at trace levels. A linear response ( R 2 >0.999), accuracy (recoveries 95.3%–101.9%), precision (RS ≤ 2.0%), sensitivity, and specificity were demonstrated by the proposed method. The approach was successfully used on commercial sertraline medication items, detecting N‐Nitroso Sertraline at levels that are within regulatory limits. The established LC‐MS/MS method is a valuable resource for routine quality control and impurity analysis of sertraline formulations due to its superior linearity, precision, accuracy, and lower detection limits compared to other methods.