New Validated LC-MS Method Development and Estimation of Nitrosamine impurities in Canaglifozin -Pub

Mohammed et al. “New Validated LC-MS Method Development and Estimation of Nitrosamine impurities in Canaglifozin”


Background: Canagliflozin is most prescribed anti-diabetic drug, as diabetic drugs are consumed daily there may be a chance of consuming nitrosamine impurities beyond their limits hence, the Food and Drug Association (FDA) recommends checking for carcinogenic impurities in routine use drugs.
Aims and Objectives: The study aims to simultaneous estimation of 4 nitrosamines (NMDA, NEIA, NIEA, and NDIPA) by liquid chromatography-mass spectrometry (LCMS) to detect the limit of detection (LoD) and limit of quantitation (LoQ). estimation of these impurities (NMDA, NEIA) in canagliflozin tablet dosage form with specificity parameters.
Methods: Drug canagliflozin was collected from hetero labs, methanol, LC-MS grade acetonitrile, formic acid four impurities (NMDA, NEIA, NDIPA, NIEA) purchased from Merck Pharmaceuticals Mumbai. The Zorbax SB C18 column (250 x 4.6 mm, 3 mcm) is used as the stationary phase, 0.1% formic acid and acetonitrile in the ratio of 70:30 is used as the mobile phase, methanol is used as diluent flow rate was maintained at 1-mL/min, the injection volume was fixed to 10 mcl, which is run at 10 minutes. The electron ionization ion source, multiple reaction monitoring, and acquisition mode is used for the study. The time required for the solvent delay and detector off is 4 and 9.5 minutes, respectively. The product ions peaks of impurities were observed at 44 for NDMA, 99 for NEIA.
Results: The %RSD for the peak areas of NDMA, NEIA obtained from six replicate injections of standard solutions were 2.5, 9.8, 1.4 and 7.7, respectively. The %recovery of NDMA and NEIA were within the limit. The %RSD for the results obtained from the method precision study was within the limit.
Conclusion: The above observations indicate that the LC-MS method meets the acceptance criteria for the parameters selected for the validation study. Hence, the method is suitable for the determination of NDMA, NEIA in a Drug Substance by LC-MS.
Keywords: Canagliflozin, Electron ionization, LC-MS method, NMDA, NDEA, NEIPA, NDIPA.

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