Advanced LC-MS/MS method for the determination of N-Nitroso Atomoxetine in Atomoxetine oral solution: Ensuring drug safety

A highly sensitive and selective LC-MS/MS method was developed and validated for the determination of N-Nitroso Atomoxetine, a potential nitrosamine impurity in Atomoxetine Oral Solution. Chromatographic separation was achieved using a reversed-phase column and a mobile phase of Acetonitrile: HPLC water: Methanol (75:20:5 v/v/v) with 0.1% formic acid. Detection was performed in positive electrospray ionization mode using multiple reaction monitoring (MRM). The method showed excellent specificity, linearity (R² = 0.9995), sensitivity (LOD: 0.1 ppb; LOQ: 0.2 ppb), and precision (RSD < 2.6%). Recoveries ranged from 104.3% to 109.2%. This validated method meets regulatory expectations for nitrosamine drug substance-related impurities (NDSRIs) and offers a robust analytical solution for quality control and risk mitigation in Atomoxetine formulations.