Development and Validation of a GC-MS/MS Method for the Determination of Genotoxic Nitrosamine Impurities in Levetiracetam Extended-Release Tablets
Keywords:
Analytical quantification, GC-MS, multiple reaction monitoring (MRM), validation, genotoxic and carcinogenic contaminants, Nitrosamine impurities, Levetiracetam etc.Abstract
A robust analytical procedure was developed and validated for the detection of genotoxic, carcinogenic, and nitrosamine contaminants in Levetiracetam ER tablets using Gas Chromatography–Mass Spectrometry (GC-MS) with Multiple Reaction Monitoring (MRM). For NEIPA, NMPA, and NDEAwith considering the 0.5g MDD for Levetiracetam Tablets acceptable intake should not be more than 0.19µg/g. The method demonstrated exceptional sensitivity, achieving a limit of quantification (LOQ) of 0.06µg/g and a limit of detection (LOD) of 0.02µg/g. Furthermore, Calibration curves exhibited strong linearity with correlation coefficients exceeding 0.99, while specificity was confirmed by minimal interference from excipients. Recovery experiments yielded results between 92.7% and 99.0%, validating the accuracy and reliability of the method. The validated approach ensures dependable monitoring of these critical contaminants, thereby safeguarding product quality, patient safety, and regulatory compliance.
