title: Identification, characterization and quantification of new impurities by LC-ESI/MS/MS and LC-UV methods in rivastigmine tartrate active pharmaceutical ingredient.
abstract: Six impurities were detected at trace level in rivastigmine tartrate drug substance by a newly developed high performance liquid chromatography method. Three impurities were characterized rapidly and three impurities were found to be unknown. The unknown impurities were enriched and identified with a combination of semi-preparative HPLC and LC/MS/MS techniques. Proposed structures were further confirmed by characterization using NMR, FT-IR, and EA techniques of impurity standards. Based on the spectroscopic, spectrometric and elemental analysis data unknown impurities were characterized as 3-[1-(dimethylamino)ethyl]phenyl N-ethyl-N-methyl carbamate N-oxide, ethyl-methyl-carbamic acid 4-(1-dimethylamino-ethyl)-phenyl ester and ethyl-methyl-carbamic acid 2-(1-dimethylamino-ethyl)-phenyl ester. A plausible mechanism for the formation of these impurities is also proposed. The method was validated according to ICH guidelines for fourteen impurities to demonstrate specificity, precision, linearity, accuracy and stability indicating nature of the method. Regression analysis showed correlation coefficient value greater than 0.999 for rivastigmine tartrate and its impurities. Accuracy of the method was established based on the recovery obtained between 93.41 and 113.33% for all impurities.
authors: Jubilant Life Sciences Ltd., Analytical Research Department, R&D Centre, C-26, Sector-59, Noida, Uttar Pradesh 201 301, India. saji_thomas@jubl.com
authors: Saji
authors: S
authors: Thomas
authors: Sanjeev
authors: S
authors: Shandilya
authors: Amber
authors: A
authors: Bharati
authors: Saroj Kumar
authors: SK
authors: Paul
authors: Ashutosh
authors: A
authors: Agarwal
authors: Chandra S
authors: CS
authors: Mathela
mesh_terms: D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D048448:Phenylcarbamates / Q000737:chemistry*; D012015:Reference Standards; D015203:Reproducibility of Results; D000068836:Rivastigmine; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D017550:Spectroscopy, Fourier Transform Infrared; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002800:Cholinesterase Inhibitors; D004364:Pharmaceutical Preparations; D048448:Phenylcarbamates; D000068836:Rivastigmine