Development and Validation of an LC–MS/MS Method for Trace‐Level Nitrosamine Analysis in Mexiletine Formulations

ABSTRACT Since 2018, genotoxic targeted nitrosamine impurity levels have been monitored and restricted as a necessary quality and safety characteristic for a number of pharmaceutical products. A highly reliable and sensitive analytical technique was created and verified in this study to quantitatively identify seven minor nitrosamines in the mexiletine formulation at low concentrations. Gradient elution employed a mobile phase A consisting of 0.1% formic acid in water. 0.1% formic acid in methanol was utilized as mobile phase‐B at a flow rate of 0.5 mL/min.·A 150 mm × 4.6 mm, 5 µm Inertsil ODS C18 column was used to achieve chromatographic separation, and the column temperature was kept at 40°C. The method was validated in accordance with USP and ICH criteria. This analysis shows linearity ( R 2 > 0.999) and a high degree of accuracy, ranging from 95.3% to 104.8%. Because it uses a methodical, statistically optimized approach for method development to guarantee robustness, accuracy, and dependability, the LC‐MS/MS technology is important for mexiletine formulations. According to the study, this method might be used not only for mexiletine capsules but also as a generic screening tool to evaluate various medicinal substances and drug products under the minimal circumstances needed for method optimization.