Trace-level quantification of NDMA in levosulpuride active pharmaceutical ingredient and tablet formulation Using UFLC-MS/MS

• UFLC-MS/MS method for the quantification of NDMA in levosulpuride API and tablets. • Developed method is selective, sensitive and reproducible. • Greenness assessment for the developed method was performed by tools like GAPI, AGREE and AES and greenness profile is also compared with analytical methods in the literature. • Suitable for regular quality control of levosulpuride products in pharmaceutical industry. Nitrosamine impurities identified in several pharmaceuticals during recent times has raised concerns leading to product recalls worldwide and necessitating sensitive liquid and gas chromatographic methods for trace level detection of nitrosamine impurities. This study developed and validated a green ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method for the quantification of NDMA in Levosulpuride drug substance and tablet formulation. The method employed a triple quadrupole analyzer, atmospheric pressure chemical ionization (APCI) ionization source and multiple reaction monitoring (MRM) scan mode for the analysis. Chromatographic separation was achieved on a Gemini NX-C18 column (150 × 4.6 mm, 3 µm) maintained at 40°C. The mobile phase consisted of a binary gradient of solvent A (0.1% formic acid in water) and solvent B (methanol), with a total run time of 18 minutes for the sensitive and specific detection of the analytes. Method validation demonstrated excellent linearity, recovery, precision, and sensitivity. The greenness of the developed analytical method was critically assessed through comprehensive evaluations using the GAPI, AGREE, and AES metrics. This novel UFLC-MS/MS method offers a reliable and sensitive approach for routine quality control analysis of Levosulpuride drug substance and tablet formulations.