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An orthogonal approach for method development and validation of three potential halo alkyl alcohol genotoxic impurities in miglitol drug substance by fast gas chromatography–mass spectrometry
Author(s) -
Rajagaraju,
Ramana D.V.,
Ganta Rama Rao,
Devi Dharamasoth Rama,
Deshpande Amol A.,
Babu J. Moses,
Basavaiah K.
Publication year - 2020
Publication title -
separation science plus
Language(s) - English
Resource type - Journals
ISSN - 2573-1815
DOI - 10.1002/sscp.202000050
Subject(s) - chemistry , alcohol , chromatography , ethanol , alkyl , detection limit , impurity , solid phase extraction , mass spectrometry , organic chemistry
Miglitol is an azasugar. It is the oral antidiabetic drug that inhibits the glucose generation from the polysaccharides and oligosaccharides. The miglitol structure includes 1‐deoxynojirimycin and ethyl alcohol, the alkyl alcohol part is a key starting material for miglitol. The moiety adds by halo alkyl alcohols such as 2‐bromo ethanol, 2‐chloro ethanol, and 2‐iodo ethanol to 1‐deoxynojirimycin. Miglitol's maximum dosage per day is 300 mg, hence any genotoxic impurity in the miglitol should control below 5 ppm. A fast gas chromatography and mass spectrometry analytical method was developed and validated for 2‐bromo ethanol, 2‐chloro ethanol, and 2‐iodo ethanol in miglitol drug substance by using DB‐1, 15 m, 0.25 mm, and 1 µm column, which constitutes the poly‐dimethyl siloxane stationary phase. The limits of detection and quantitation were achieved at 0.7 and 2.0 ppm, respectively. The recoveries were from 81.7 to 118.8% for all impurities. The method was linear from 2.0 to 15 ppm for all impurities and their correlation coefficient values were in the range of 0.992–0.996. The method was precise at limit of quantitation (2.0 ppm), 2.5, 5.0, and 7.5 ppm levels, the %RSD values were <13.5%, and analytical solutions were stable at 25˚C.