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

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 mu m 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 25C.