In silico toxicity assessment and trace level quantification of two genotoxic impurities in silodosin using capillary gas chromatography

Abstract

AbstractA capillary gas chromatographic method using flame ionization detection was developed and validated for the trace quantification of 2-bromoethanol (2-BE) and 2-bromoethylmethanesulfonate (2-BEM) in silodosin, used in the treatment of benign prostatic hyperplasia. Chromatographic separation was performed in spilt mode using nitrogen as carrier gas on a column containing crosslinked polyethylene glycol (30 m × 0.32 mm, 0.25 µm) stationary phase modified with nitroterephthalic acid. A simple matrix precipitation strategy was implemented to eliminate the sample overload and the matrix interference problems. The developed method was linear and accurate in the concentration range of 24–3000 ppm for 2-BE and 24–300 ppm for 2-BEM with r2 ˃ 0.999 and percent recoveries greater than 90% for both the analytes. The developed method was precise for both the analytes with RSD(%) of not more than 4.5%. In silico genotoxicity and carcinogenicity potential of 2-BEM were assessed using ICH M7 principles. The developed method can be applied in the quality control laboratories of pharmaceutical industries for trace level quantification of 2-BE and 2-BEM in silodosin.