Development and Validation of Residual Amount of Potential Genotoxic Substance 1-Bromo-2-Methylpropane in Febuxostat by GC

Abstract

In the present work, an effective and sensitive gas chromatography (GC) method for determination of the residual solvent 1-Bromo-2 Methylpropane in febuxostat was developed using an Agilent DB-624 column (30 m × 0.53 mm × 3.0 μm) and an optimized oven program. Its working range, linearity, the limit of detection (LOD) and the limit of quantification (LOQ), accuracy, precision, robustness, and stability were measured to verify the method. The LOD and the LOQ was 0.4725 μg/mL and 0.9450 μg/mL, respectively. The method has a wide working range of 0.9450 μg/mL (1.89ppm) ~ 21.6216μg/ mL (43.24ppm) for 1-Bromo-2-Methylpropane. And the method has a good linearity with the regression coefficient of the calibration graphs was 0.9998. The accuracy was determined by the recovery rate (80%, 100%, 120%) of three concentration levels, which were in the range of 96.04 to 102.93 %. Precision was expressed as a percentage of relative standard deviation (%RSD), which was 1.34% for determined 1-Bromo-2-Methylpropane. The results showed that the developed GC method had the great specificity, linearity, accuracy and precision, and applicable for the low-level detection of 1-Bromo-2-Methylpropane in febuxostat. This method can provide a new choice for GC determination of potential genotoxic impurities in febuxostat.